Bacteria Genomes Are Degrading

 
At one point in his talk last night Kirk Durston mentioned the bacterial flagella. He acknowledged that the "Darwinists" have proposed an evolutionary pathway from a Type III secretory structure to flagella.

This pathway is improbable, according to Durston, because flagella are more complicated than secretory pores so flagella have to evolve first.

What? Yes, that's right. Scientists have now shown that the most primitive bacteria were very complex and evolution has been all downhill from then on. Modern bacteria are less complex. Thus the type III secretory apparatus had to evolve from the more complex bacterial flagella. (The actual situation is complicated [Evolution in (Brownian) space: a model for the origin of the bacterial flagellum]. What I'm addressing here is the claim of general loss of information in bacterial evolution.)

I suggested that this was bull not correct and Durston responded with a slide showing the scientific papers that proved it. The most important paper was

Mira, A., Ochman, H. and Moran N.A. (2000) Deletional bias and the evolution of bacterial genomes. Trends Genet. 17:589-96. [PubMed]

I asked Durston what would happen if I called Nancy Moran (no relation, that's her above) and asked her whether she agreed that primitive bacteria were complex and all modern bacterial lineages are losing information. He affirmed that she would and that's what modern evolutionary biologists are saying. There are other papers that say the same thing. He accused me of not being aware of them.

This is the abstract of the Mira et al. (2000) paper.

Although bacteria increase their DNA content through horizontal transfer and gene duplication, their genomes remain small and, in particular, lack nonfunctional sequences. This pattern is most readily explained by a pervasive bias towards higher numbers of deletions than insertions. When selection is not strong enough to maintain them, genes are lost in large deletions or inactivated and subsequently eroded. Gene inactivation and loss are particularly apparent in obligate parasites and symbionts, in which dramatic reductions in genome size can result not from selection to lose DNA, but from decreased selection to maintain gene functionality. Here we discuss the evidence showing that deletional bias is a major force that shapes bacterial genomes.

I think it's pretty obvious from the abstract that they're discussing a particular problem in bacterial evolution; namely selection for small compact genomes. This point is clear in the paper as well.

At no point in the paper do the authors suggest anything close to what Durston says. There's no mention of primitive bacteria having the full complexity of all modern species including the myxobacteria and photosynthetic bacteria etc. Why in the world do the Intelligent Design Creationists have to lie about things like this? (I assume it's a lie because the only other possibility is ignorance and a Ph.D. student in biophysics can't be stupid enough to misunderstand such a key principle of evolution, right?)

Naturally in a forum like this Durston had me at a disadvantage. He was displaying the scientific papers and I had to admit that I had not read them recently enough to comment. The point was not lost on some members of the audience. The atheist scientist was trumped by the religious graduate student who was more aware of the scientific literature.

"Frustrating," doesn't begin to cover it ...

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Kirk Durston's Proof of God

 
I went to the lecture in Denyse O'Leary's course last night [I'm Going to a Lecture on Intelligent Design]. As promised, the guest speaker was Kirk Durston, a graduate student in biophysics at the University of Guelph.

It was a very frustrating experience. Like most Intelligent Design Creationists, Durston was all over the map in terms of spreading lies and misconceptions about science. This scattergun approach seems to be very successful for them. I assume it's because no one person can address all of the problems with their presentation. Most people will catch one or two flaws but they'll assume that everything else has to be correct.

I'll come back to some of these lies in another posting but right now I'd like to explain his main argument.

Kirk Durston has a background in computer science and his project has to do with analyzing the sequences of conserved gene families.

The Intelligent Design Creationist part of his study relies heavily on the work of Douglas Axe (Axe, 2000; Axe, 2004). Axe is head of Biologic Institute a "research" company in Redmond, WA (USA) with ties to the Discovery Institute [We're in Trouble Now].

The papers Axe published in the prestigious Journal of Molecular Biology represent work he did as a post-doc in Cambridge UK. The goal was to show that the probability of a protein adopting a particular three-dimensional fold is very, very low.

Durston is pursuing this line of work and he described it in his talk last night with plenty of equations and diagrams. There were about 15 people in the room and it's almost certain that nobody other than me had any idea what was going on. But it all sounded very sophisticated.

As it turns out, not understanding the science shouldn't have been such a big deal since the form of his argument was obviously silly. At least I thought it was obvious. Here's the way it went ...

1. By making assumptions A, B, C, and D and constructing equations E and F he is able to predict that no protein will have more than X amount of information.


2. By making a few assumptions about protein families it is possible to measure the amount of information in a folded domain by plugging the data into his equations. It turns out that most proteins have more than X information.


3. Therefore God exists (i.e., the protein must have been intelligently designed).

This are (at least) two major flaws in this argument and it doesn't take an expert in computer science or biochemistry to detect them.

First, when you formulate a scientific hypothesis you test it against scientific reality. If the predictions of your hypothesis are not fulfilled then your hypothesis is falsified. At that point it's back to the drawing board. You need to reconsider your assumptions or your equations because they were not successful. That's how science is done but that's not how Intelligent Design Creationism is done.

Second, the sudden appearance of God in the conclusion is illogical. There's no mention of God intelligent design in the premise. It just pops out of the argument without any warning. This is not how logic works and it's certainly not how science works.

I tried to point this out last night but nobody in the audience was paying attention and Durston was in no mood to discuss logic after having spent close to two hours practicing something else.

We have a word to describe people who can't construct a simple logical argument. It seems to have slipped my mind .... what is it ..... oh, yeah, now I remember ... IDiot.

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Axe, D. (2000) Extreme Functional Sensitivity to Conservative Amino Acid Changes on Enzyme Exteriors. J. Mol. Biol. 310:585-595.

axe, D. (2004) Estimating the Prevalence of Protein Sequences Adopting Functional Enzyme Folds. J. Mol. Biol. 341:1295-1315.

Nobel Laureates: Konrad Bloch and Feodor Lynen

 

The Nobel Prize in Physiology or Medicine 1964.

"for their discoveries concerning the mechanism and regulation of the cholesterol and fatty acid metabolism"

Konrad Bloch (1912-2000) and Feodor Lynen (1911-1979) received the Nobel Prize in Physiology or Medicine for their work in deciphering the cholesterol biosynthesis pathway.

Feodor Lynen is mainly responsible for working out the pathway from acetate (acetyl CoA) to mevalonate [How Lipitor® Works] while Konrad Bloch worked mostly on the rest of the pathway [How to Make Cholesterol][Making Squalene].

Last week's Nobel Laureate, John Cornforth, was rewarded for discovering the exact mechanisms that give rise to a stereospecific product [Nobel Laureate: John Cornforth].

The 1964 presentation speech was given by Professor S. Bergström, member of the Nobel Committee for Physiology or Medicine of the Royal Caroline Institute.

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen.

Since the start of the Nobel Foundation the professorial staff of the Karolinska Institute has chosen the prizewinners in Physiology or Medicine. This year the Karolinska Institute has been reorganized into a medical university and the duties of the professorial staff have been taken over by the medical faculty of the enlarged Karolinska Institute. As the last item on its agenda the professorial staff was to decide this year's Nobel Prizewinners in Physiology or Medicine and on October 15 Professors Konrad Bloch and Feodor Lynen were awarded the prize for their discoveries concerning the mechanism and regulation of the cholesterol and fatty acid metabolism.

The word cholesterol means gallstone and the reason for this name is that cholesterol was isolated almost 200 years ago from human gallstones. Another connection between cholesterol and human diseases has been established more recently. During the last decade there has been a lively discussion, also in the newspapers, about the correlation between atherosclerosis and the amount of cholesterol and other fats in diet and in blood. This discussion has perhaps concealed from many the fact that cholesterol is a necessary constituent of all our cells and that it fulfills important functions. The elucidation of its chemical structure is one of the foremost achievements in organic chemistry during the 1910's and 1920's. In 1928 the German chemists Windaus and Wieland received Nobel Prizes in Chemistry for their work on the structure of cholesterol and the closely related bile acids. The four-ring carbon skeleton characteristic of cholesterol was later found not only in a number of sterols of plant and animal origin but also in the precursors of vitamin D, in the male and female sex hormones, in the hormones from the adrenal cortex, etc.

Nothing was known about the way they were formed or about their interrelationships. When this year's prizewinners started their scientific career, Professor Hevesy had done his discoveries concerning the use of isotopes as tracers in the living organism. When first the stable and later the radioactive isotopes of hydrogen and carbon became available, they were first extensively used by a group at Columbia University that was headed by the late Rudolph Schoenheimer and in which Bloch played an important role. The work of the group with isotopically labeled compounds has laid the foundation of our general knowledge of the dynamic state in the living cell.

One of the fundamental discoveries was the elucidation of the role of acetic acid as a building block for cholesterol as well as fatty acids. Lynen, working in Wieland's laboratory on the metabolism of acetic acid, succeeded in isolating the so-called activated acetic acid, which is the precursor of all lipids in our body and the common denominator of a number of metabolic processes. With all possible refinements in the utilization of isotope techniques, Bloch and collaborators were able to show in a series of brilliant investigations how the two carbon atoms of acetic acid are used for the synthesis of a long hydrocarbon with thirty carbon atoms, squalene, which in turn is cyclized in a novel type of reaction to a steroid with thirty carbon atoms, lanosterol. This lanosterol is then transformed in a complicated series of reactions into cholesterol, which has twenty-seven carbon atoms. Of special interest are the reactions leading to the formation of the hydrocarbon squalene, and the elucidation of these reactions, which are common for the biosynthesis of many other lipids and natural products, is due not only to Bloch and Lynen and collaborators but also to Popjak and Cornforth in England and Folkers and co-workers in the U.S.A. In connection with this work Lynen made two other discoveries of great importance to our understanding of the mechanisms of cellular metabolism: the elucidation of the mechanism of action of the vitamin biotin and the determination of the structure of cytohemin.

At an early stage Bloch made another discovery of fundamental importance in showing that cholesterol is the precursor of bile acids and of one of the female sex hormones. These discoveries opened up a new field of research that has engaged a great number of scientists in different disciplines. We know now that all substances of steroid nature in our body are formed from cholesterol.

Mainly through the basic biochemical work of this year's prizewinners do we know today in detail how cholesterol and fatty acids are synthesized and metabolized in the body. These processes comprise series of reactions with a great number of individual steps. For instance, the formation of cholesterol from acetic acid is a process involving some thirty different steps. Derangements of this complicated mechanism of formation and metabolism of lipids are in many cases responsible for the genesis of some of our most important diseases, especially in the cardiovascular field. A detailed knowledge of the mechanisms of lipid metabolism is necessary to deal with these medical problems in a rational manner.

The importance of the work of Bloch and Lynen lies in the fact that we now know the reactions which have to be studied in relation to inherited and other factors. We can now predict that we, through further research in this field in the near future, can expect to be able to do individual specific therapy against the diseases that in the developed countries are the most common cause of death.



Professor Bloch, Professor Lynen. You have both started your research in Munich and you have proceeded the proud tradition of this town in a splendid way.

Feodor Lynen, you are now standing with dignity in the array of the earlier Munich Nobel Prizewinners, Adolf von Baeyer, Hans Fischer and Heinrich Wieland.

Konrad Bloch, you have like Emil Fischer and Richard Willstätter left Munich and continued your work in the New World.

I have made a very short summary of your successful research work in the field of lipids. You have provided us with detailed knowledge of many fundamental metabolic reactions. This knowledge forms the necessary basis for the study of the different medical problems in the field of lipid metabolism.

It can now be anticipated that in the near future we will learn how to deal with many of these diseases in a rational and successful way.

On behalf of the Caroline Institute I have the honour to congratulate you on your brilliant work and I now ask you to receive your prizes from the hands of His Majesty the King.

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[Photo Credits: Konrad Bloch plaque is from Wikipedia. Restricted photos of Feodor Lynen are available on ViewImages]

Best Lab Website

 
New Scientist is running a contest for the best laboratory website. The ten finalists are listed on the New Scientist website [Laboratory Website and Video Awards].

One of the finalists is the lab website of T. Ryan Gregory of Genomicron [Please vote for my lab website.].

Now, I'm not saying that you should hop on over to the New Scientist site and vote for Ryan Gregory just because he's such a nice guy and he's a blogger. And certainly not just because it's a Canadian lab. Of course you shouldn't do that. This is a legitimate scientific poll and heaven forbid that there would be any shenanigans in the voting. No siree, Bob.

You should carefully examine each and every one of the ten finalists and make an honest judgment about the best site. I choose Ryan Gregory's lab site as my #1 pick. If you don't want to waste time you can trust me and vote for him too. Pick the Emili lab site as your #2 choice 'cause Andrew Emili is a colleague of mine has the next best site.

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[Photo Credit: Gregory Lab: Genomic Diversity]

Two Cultures

Stephen Fry has posted a long description of a debate he had with an American aquaintance about global climate change [Getting Overheated]. You should read the whole thing but there's one part that caught my eye.

We must begin with a few round truths about myself: when I get into a debate I can get very, very hot under the collar, very impassioned, and I dare say, very maddening, for once the light of battle is in my eye I find it almost impossible to let go and calm down. I like to think I’m never vituperative or too ad hominem but I do know that I fall on ideas as hungry wolves fall on strayed lambs and the result isn’t always pretty. This is especially dangerous in America. I was warned many, many years ago by the great Jonathan Lynn, co-creator of Yes Minister and director of the comic masterpiece My Cousin Vinnie, that Americans are not raised in a tradition of debate and that the adversarial ferocity common around a dinner table in Britain is more or less unheard of in America. When Jonathan first went to live in LA he couldn’t understand the terrible silences that would fall when he trashed an statement he disagreed with and said something like “yes, but that’s just arrant nonsense, isn’t it? It doesn’t make sense. It’s self-contradictory.” To a Briton pointing out that something is nonsense, rubbish, tosh or logically impossible in its own terms is not an attack on the person saying it – it’s often no more than a salvo in what one hopes might become an enjoyable intellectual tussle. Jonathan soon found that most Americans responded with offence, hurt or anger to this order of cut and thrust. Yes, one hesitates ever to make generalizations, but let’s be honest the cultures are different, if they weren’t how much poorer the world would be and Americans really don’t seem to be very good at or very used to the idea of a good no-holds barred verbal scrap. I’m not talking about inter-family ‘discussions’ here, I don’t doubt that within American families and amongst close friends, all kinds of liveliness and hoo-hah is possible, I’m talking about what for good or ill one might as well call dinner-party conversation. Disagreement and energetic debate appears to leave a loud smell in the air.

I understand this difference. Here in Canada we're half way between Europe and America in terms of debate tactics. In some cases you can have lots of fun carrying on in a "British" tradition. But from time-to-time you encounter some people from the "American" cultural tradition and they take great offense at such behavior.

The problem is especially acute when dealing with creationists. They are very good at politely lying and spreading misinformation with a pleasant smile on their faces. They are ever so respectful of the "other side" while, at the same time, implying that all scientists are really stupid.

But when you try and call them on their lies you are immediately dismissed for being rude and uncivilized. The average "Christian" will only tolerate polite discourse and by that they mean non-confrontational. As long as you tells lies in a quiet polite voice it's okay.

We also see the problem when discussing militant atheists. People like Richard Dawkins and Christopher Hitchins are just behaving normally in the culture in which they were raised. It's Americans who see this as a particularly disrespectful way of behaving. That's why American atheists are so often opposed to the so-called militant atheists and think they're hurting the cause.

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[Hat Tip: RichardDawkins.net]

[Photo Credit: stephenfry.com]

How Lipitor® Works

 
In previous postings we learned how cholesterol is made from squalene and squalene is made from the six carbon compound mevalonate [How to Make Cholesterol] [Making Squalene].

Today we'll cover the synthesis of melavonate from three molecules of the 2-carbon compound acetate.

When acetate is involved in biosynthesis reactions it is "activated" by forming a thioester linkage to coenzyme A ("thio" means sulfur). Coenzyme A was discovered by Nobel Laureate: Fritz Lipmann.

The first step in the pathway is the joining of two molecules of acetyl CoA to make the 4-carbon compound acetoacetyl CoA. Note that this molecule is still joined to coenzyme A. In the second step, another acetyl group is transferred to acetoacetyl CoA to make the 6-carbon molecule 3-hydroxyl-3-methylglutaryl CoA (HMG CoA). HMG-CoA was Monday's Molecule.

The last step is cleavage of the thioester linkage between the 6-carbon compound and CoA releasing mevalonate.

This last step is catalyzed by an enzyme called HMG-CoA reductase. This is an oxidation-reduction reaction where the reduction of HMG-CoA is coupled to the oxidation of NADPH. This enzyme is regulated inside the cell and this controls the biosynthesis of cholesterol since mevalonate is an essential intermediate in the pathway.

Lipitor® and similar drugs control cholesterol synthesis by inhibiting the enzyme HMG-CoA reductase. If we draw the substrate in a way that shows its structure, you can see that Lipitor® and Mevacor® resemble the business end of the molecule—the part that's cleaved by the enzyme. These drugs are effective inhibitors because they bind to the active site of the enzyme.



The class of HMG-CoA reductase inhibitors is called statins. They are used to control serum cholesterol levels in the hopes of reducing the risks of coronary heart disease. There don't seem to be any serious side effects to inhibiting mevalonate production in spite of the fact that mevalonate is required for synthesis of some hormones and of the essential cofactor ubiquinone [Ubiquinone and the Proton Pump].

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Parental Guidance Suggested

 

This rating was determined based on the presence of the following words:

* dead (2x)
* sex (1x)

I wonder what kind of rating I would get if Sandwalk were rated in France? Do they have a "milquetoast" rating?

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Swift Boat Funder T. Boone Pickens Reneges On John Kerry Million Dollar Offer

 
Anyone who spoke out against the war in Viet Nam and who knew Jane Fonda would get my vote. Especially if the other choice was someone who didn't even like Jane Fonda.

Do you remember the Swift Boat campaign against John Kerry? You should. It's going to be important in the next year since we're very likely to see something similar in the next Presidential election campaign.

One of the founders of Swift Boat Veterans for Truth (sic) has just offered one million dollars if Kerry can prove that there was even one lie in the ads they placed on television. Kerry takes up the challenge but, it seems as though there's some fine print ... [ Swift Boat Funder T. Boone Pickens Reneges On John Kerry Million Dollar Offer]. Imagine that.

Pickens supports Rudy Giuliani so it's unlikely that Giuliani will be swiftboated. Hmmm, I wonder who the target will be ....

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[Hat Tip: Canadian Cynic]

I'm Going to a Lecture on Intelligent Design

 
Denyse O'Leary is teaching a course on Intelligent Design at the University of St. Michael's College, University of Toronto [Denyse O'Leary's University Course on Intelligent Design].

The outline of the course was posted on Post-Darwinist [ COURSE: By Design or by Chance? An introduction to the intelligent design controversy].

Students in the course are allowed to invite a guest for one lecture and one of my friends, who shall remain nameless for now, has urged me to come along. By all accounts the course is going well and Denyse is presenting both sides of the controversy.

Tonight's lecture is ...

Session 5. Intelligent design: What the ID proponents actually say (and don’t say) Tuesday November 20, 2007

Michael Behe, author of Edge of Evolution (2007), sees actual design where, for example, Richard Dawkins, author of The Blind Watchmaker, sees the illusion of design. Who’s right? Are they both wrong?

Guest: Kirk Durston, biophysics PhD candidate at the University of Guelph.

Kirk Durston (right) is the National Director of the New Scholars Society. According to his biography on their website,

KIRK DURSTON, B.Sc (Physics), B.Sc. (Mech. Eng.), M.A. (Philosophy), Ph.D. Candidate (Biophysics) at the University of Guelph.

Kirk Durston is the National Director of the New Scholars Society. He is currently a Ph.D. candidate in Biophysics at the University of Guelph, specializing in the application of information to biopolymers. His other interests include amateur astronomy, wilderness canoeing & camping, and landscape photography & art.

What is it about creationists that they always seem to have multiple redundant degrees? In this case he has two Bachelor's degrees. What's with that?

It's easy to find out what Kirk believes because there's a Statment of Faith on the website.

The sole basis of our beliefs is the Bible, God's infallible written Word, the 66 books of the Old and New Testaments. We believe that it was uniquely, verbally and fully inspired by the Holy Spirit, and that it was written without error (inerrant) in the original manuscripts. It is the supreme and final authority in all matters on which it speaks.We accept those large areas of doctrinal teaching on which, historically, there has been general agreement among all true Christians. Because of the specialized calling of our movement, we desire to allow for freedom of conviction on other doctrinal matters, provided that any interpretation is based upon the Bible alone, and that no such interpretation shall become an issue which hinders the ministry to which God has called us.

Jeffrey Shallit had a few things to say about Kirk Durston on Recursivity [Kirk Durston: Apologist for Genocide]. This is going to be an interesting lecture.

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Who Was Adam?

 
One of the regular contributers to the comments section of Sandwalk has suggested we read Who Was Adam? by Fazale Rana and Hugh Ross. Apparently this is a very good explanation of how evolution is compatible with the Bible.

Hugh Ross is the ruler of Reasons to Believe, an organization that promotes the integration of science and fundamentalist Christianity. Here's part of their Statement of Faith.

We believe the Bible (the 66 books of the Old and New Testaments) is the Word of God, written. As a "God-breathed" revelation, it is thus verbally inspired and completely without error (historically, scientifically, morally, and spiritually) in its original writings. While God the Holy Spirit supernaturally superintended the writing of the Bible, that writing nevertheless reflects the words and literary styles of its individual human authors. Scripture reveals the being, nature, and character of God, the nature of God's creation, and especially His will for the salvation of human beings through Jesus Christ. The Bible is therefore our supreme and final authority in all matters that it addresses.

Fazale (Fuz) Rana is a biochemist who works for Hugh Ross at Reasons to Believe.

I've seen Hugh Ross in action when he was here for a two day symposium organized by Denyse O'Leary and some of her friends. Hugh Ross is a genuine kook with nothing to say that's even remotely interesting to scientists. I don't know about Fazale Rana. Has anyone read this book?

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Gene Genie #20

 

The 20th edition of Gene Genie has just been published on Bitesize Bio [Gene Genie #20].

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Genetically Speaking All Races Are Equal

 
That's what the genetics expert, Crystal, told us in her video [Crystal Tells Us about the Human Genome] ...

Now, surprisingly enough, genetically speaking all races are equal. As a matter of fact, if you took a random sample of someone's DNA, just by looking at it you could not tell whether they were African-American, Caucasian, Asian or any other race.

I guess Crystal forgot to tell Price et al. (2007) because this is what they say in the abstract of the paper they just published in PLoS Genetics ...

European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false positive or negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data.

So, not only can we distinguish Caucasians from Africans and Asians, we can also sort out different groups within Caucasians.

Isn't it amazing that scientists can do this when there's no genetic differences between races?

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Price, V. et al. (2007) Discerning the ancestry of European Americans in genetic association studies. PLoS Genet. In press. [doi:10.1371/journal.pgen.0030236.eor]

Judgment Day Online

 
Judgment Day is the PBS Nova show about the Dover trial. You can now watch it online in 12 episodes [Judgment Day].

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[Hat Tip: Monado at Science notes ( "Intelligent Design on Trial" comes to your computer)]

A World Without Writers

 

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[Hat Tip: Canadian Cynic]

Monday's Molecule #52

 
Today's molecule is a bit more complicated than some. Most of you probably haven't encountered it in your studies and those who have may have seen it drawn a bit differently. Your task is to give it a complete biochemical name as well as the shortened common name.

There's a direct connection between this molecule and Wednesday's Nobel Laureate(s).

The reward goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous winners are ineligible for one month from the time they first collected the prize. There are three ineligible candidates for this week's reward. The prize is a free lunch at the Faculty Club.

Send your guess to Sandwalk (sandwalk(at)bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and the Nobel Laureate(s). Correct responses will be posted tomorrow along with the time that the message was received on my server. I may select multiple winners if several people get it right.

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

UPDATE: We have a winner! The molecule is 3-hydroxy-3-methylglutaryl-Coenzyme A, or HMG-CoA. Wait to see who the Nobel Laureate is tomorrow.

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