Gerald Ford

 
One of my theist friends, Denny Cochran, took this picture of the planes that flew over the Gerald R. Ford Museum in Grand Rapids during the funeral on Wednesday. The flight is following the Grand River from Lake Michigan. According to Denny, the lead planes are right over the Museum.

The services were very moving even for a Canadian. I was living in the USA when Ford became Vice-President and I always thought he was good for the country.

One of the things that surprised me about the funeral sevices in Washington was the prominent presence of the military. I guess that's to be expected when a former commander-in-chief dies.

Iraqis say they were better off under rule of Saddam Hussein

 
Iraq Centre for Research and Strategic Studies/Gulf Research Center conducted face-to-face interviews with 2,000 Iraqi adults living in major cities. The interviews were conducted in November 2006. The margin of error in such a poll is 3.1%.

According to GlobalResearch.ca the results for the question "Do you feel the situation in the country is better today or better before the U.S.-led invasion?" are:

                    Better today      5%
                    Better before    90%
                    Not sure            5%

Let's hope this puts an end to the oft-repeated myth that the Iraqis are better off after the American invasion than they were under Saddam Hussein. They don't think so.

[Hat Tip: Rhosgobel: Radagast's home]

Prostaglandin Synthesis

Eicosanoids are a class of compounds that mediate a variety of cellular responses. One group of eicosanoids is called prostaglandins. These compounds are produced by all cells and they cause the inflamatory reponse to injury and the production of pain and fever. They act like hormones and are often called hormones. They differ from true hormones in that they are produced by all cells and act locally.

Prosaglandins are made by cyclizing a 20 carbon polyunsaturated fatty acid called arachidonate. Recall that arachidonate is made from lineolate and we need to absorb linealoate from food because we can't make it ourselves. The most important reaction is the first one in the pathway. It is catalyzed by prostaglandin H synthase (PGHS) a key target for pain relief.

PGHS is a bifunctional enzyme, which means it carries out two separate reactions. The first reaction is a cyclization reaction converting arachidonate to a hydroperoxide called prostaglandin G₂. This activity is often called a cyclooxygenase (COX) activity. The second reaction is catalyzed at a different site, the hydroperoxidase site, and the final product is prostaglandin H₂.

Subsequent reactions lead to the synthesis of other prostaglandins and other eicosanoids. This is the pathway that earned Bergström, Samuelsson, and Vane the Nobel Prize in 1982.

How Painkillers Work

One way to reduce pain and fever is to inhibit prostaglandin synthesis. The ancient Greeks did this by chewing on the bark of willow trees. It turns out that willow tree bark is a natural source of salicylates and these compounds inhibit the COX acivity of prostaglandin H synthase (PGHS) by modifying the enzyme to prevent arachidonate from binding to the active site.

Unfortunately, most salicylates taste horrible and cause inflammation of the mouth, throat, and stomach. Furthermore, they block the synthesis of other prostaglandins that promote blood clotting so an excess of salicylates will lead to bleeding of ulcers and other problems.

Aspirin is a modified salicylate. The active ingredient is called acetylsalicylic acid. It was introduced as a commercial drug in 1887. It doesn't taste as bad as most other salicylates and doesn't produce severe side effects.

Although it's better than natural salicylates, aspirin can cause dizziness, ringing in the ears, and bleeding or ulcers of the stomach lining. The stomach problems are caused by inhibition of a different COX activity from the one leading to prostaglandin synthesis.

There are two different forms of PGHS or COX. COX-1 is a constitutive enzyme that regulates secretion of mucin in the stomach, thus protecting the gastric wall. COX-2 is an inducible enzyme that promotes inflammation, pain, and fever. Aspirin inhibits both isozymes.

There are many other nonsteroidal anti-inflammatory drugs (NSAIDS) that inhibit COX activity. Aspirin is the only one that inhibits by covalent modification of the enzyme. The others act by competing with arachidonate for binding to the COX active site. Ibuprofen (Advil®), for example, binds rapidly, but weakly, to the active site and its inhibition is readily reversed when drug levels drop. Acetaminophen (Tylenol®) is an effective inhibitor of COX activity in intact cells.


Physicians would like to have a drug that selectively inhibits COX-2 and not COX-1. Such a compound would not cause stomach irritation. A number of specific COX-2 inhibitors have been synthesized and many are currently available for patients. These drugs, while expensive, are important for patients with arthritis who must take pain killers on a regular basis. In some cases, the new NSAIDS have been associated with increased risk of cardiovascular disease and they have been taken off the market. X-ray crystallographic studies of COX-2 and its interaction with these inhibitors have aided the search for even better replacements for aspirin without the cardiovascular side effects.

[Modified from Horton et al. Principles of Biochemistry ©Pearson Prentice Hall]

A Confused Philosopher

Darwinism and Its Discontents, by Michael Ruse, Cambridge University Press (2006)

Ruse defines Darwinism as the idea that natural selection is the chief causal process behind all organisms (p.2). He identifies a whole list of people who oppose Darwinism. Some of these are creationists—this book is not about them.

The main "discontents," according to Ruse, are misguided social scientists with their irrational fear of genetic determinism; philosophers who "can't handle the awful truth;" and evolutionary biologists whose objections "cannot be grounded purely in theory or evidence" (p.3). Many of discontent evolutionary biologists are (gasp!) Marxists.

I am one of those scientists who question Darwinism, so this book is all about me.

What does Michael Ruse have to say about us "discontents?"

At the risk of damning myself in the eyes of sound scholarship and of God, let me be categorical. All of the critics of Darwinism are deeply mistaken.

Wrong. It is Michael Ruse who is mistaken and this damn book is full of sloppy scholarship.

Chapters 1-4 cover the basic facts of evolution. Ruse establishes the important contribution of Darwin in discovering natural selection. He points out that natural selection is the "single best idea anyone ever had" (Dennett, 195). I agree.

The "fact" of evolution is explained and the history of life is briefly described. None of this is controversial as far as scientists are concerned but Ruse is setting the stage for the most important part of the book.

Before continuing, it's worth pointing out one of the major failings of the book: the lack of any solid definition of evolution. It seems clear that Ruse is confused about the difference between evolution and one of the main mechanisms of evolution, namely, natural selection. This confusion haunts the last part of the book and makes it very difficult for Ruse to come to grips with the ideas of the "discontents."

Chapter 5 ("The Cause of Evolution") is all about natural selection. Ruse builds the case for natural selection using all the old examples that we are familiar with. Only in Chapter 6 ("Limitations and Restrictions") does he begin to address the objections to classical Darwinism.

First in the dock is adaptationism as a flawed strategy. The adaptationist fallacy is a direct frontal attack on old-fashioned Darwinian thinking. The attack was first launched by Gould and Lewontin in the famous Spandrels of San Marco paper (1979). What does Ruse have to say about this?

Now, what is to be said by the Darwinian in response to this charge? Simply this: whoever doubted the point that Gould and Lewontin are making? It has always been recognized by evolutionists—certainly from the "Origin of Species" on—that however common or ubiquitous adaptation may be, it is only part of the story. (p.135)

Bravo! In two sentences Michael Ruse admits there's more to evolution than natural selection and, therefore, the discontents have a good case. Now let's see if he understands what these other things are and why they are important. (Don't hold your breath.)

Several examples follow. In all of them, Ruse makes the case that adaptation isn't necessarily optimal. Sometimes there just hasn't been enough time for adaptation to succeed, this is why some bird species haven't yet adjusted to being parasitized by cuckoos. Sometimes natural selection has done a good, but not perfect, job; as in the circuitous route followed by mammalian sperm ducts that loop over the ureter. Sometimes natural selection is even maladaptive, as in the large antlers of the extinct Irish Elk. All of these examples are intended to show that Gould and Lewontin were wrong.

What about group selection? That's a major challenge to Darwinism and natural selection. Not a problem. Hamilton solved it by coming up with kin selection. Kin selection has been the greatest gift to adaptationist thinking since natural selection itself.

What about random genetic drift? Now, that's a real issue since there's very little doubt about its importance. (It's by far the main mechanism of evolution, properly defined.) Does Ruse agree? Nope. Ruse notes that random genetic drift was first proposed by Sewall Wright back in 1931 and expanded by Moto Kimura in 1968. But after some initial excitement Ruse concludes,

Wright's theory is not very Darwinian. Natural selection does not play an overwhelming role. Genetic drift is the key player in Wright's world. However, although many of these ideas were taken up by later thinkers, especially by Theodosuis Dobzhansky in the first edition of his influential "Genetics and the Origin of Species," drift soon fell right out of fashion, thanks to discoveries that showed that many features formerly considered just random are in fact under tight control of selection. Today no one would want to say that drift (at the physical level) is a major direct player, although in America particularly, there has always been a lingering fondness for it. (p.150)

There you have it. One of the most decisive and well studied alternatives to natural selection is dismissed as a fad. This is sloppy scholarship. Ruse clearly does not know what he's talking about. He's probably read too much of Richard Dawkins and his fellow philosopher Daniel Dennett, and not enough evolutionary biology textbooks.

Now we turn to punctuated equilibria. If Ruse is an opponent of Gould you would expect to see the standard references to saltation in this part of the book. You won't be disappointed. Although saltation and hopeful monsters have nothing to do with punctuated equilibria—and certainly nothing to do with the challenge to Darwinism—they are obligatory strawmen whenever you want to discredit Stephen Jay Gould. It's another indicator of poor scholarship.

Species selection, the real hierarchical challenge to Darwinism, isn't even mentioned. This omission is all the more remarkable since Ruse recognizes that in order to make a case for evolution at higher levels a non-Darwinian mechanism is needed; one that will decouple macroevolution and microevolution.

[Gould proposes] that at upper levels there are other mechanisms that the microevolutionists miss. Which of course might be so, but until some convincing alternatives are supplied, Darwinians continue to argue that in important respects macroevolution is microevolution writ large. Natural selection working on random mutation is the key to evolutionary change, long term as well as short term. (p.159)

What a remarkably crude way of dismissing all the work done by a large number of paleontologists, not to mention a 1433 page book called The Structure of Evolutionary Theory. Ruse may have good reason for rejecting species selection but we'll never know. Sloppy scholarship, Ruse should be ashamed.

Chapter 6 is the most important chapter since it covers the main objections of the discontented. Ruse fails to meet any of those objections; indeed, he fails to understand most of them. The rest of the book doesn't get any better.

I'll finish this off by quoting from the concluding paragraph of Chapter 6.

What is our end point? It is just plain silly to say that Darwinism is an exhausted paradigm or that selection is a trivial cause of change—or even that it calls for significant revision or augmentation. It is a powerful mechanism and has proven its worth time and time again. It is not all-powerful. Natural selection has its limits—limits that have been recognized since the time of Darwin (he himself noted many of them)—but taken as a whole, it is the key to understanding the organic world. There is no call for theory change yet, nor is there any prospect of such change in the near future. (p.165)

Speaking for the discontents, I beg to differ. Random genetic drift is by far the most common mechanism of evolution and modern evolutionary theory fully acknowledges this fact. Darwinism (natural selection) is important but it ain't the only game in town. Darwin knew nothing about random genetic drift. That's why it's wrong to describe modern evolutionary theory as Darwinism.

Gould and his colleagues have proposed a hierarchical theory of evolution in which natural selection is only one mechanism and it operates at only one level (individuals within a population). Hierarchical theory may not be correct but you'll never know from reading this damn book.

Happy Perihelion Day!

Today's the day we are closest to the sun.

It's the warmest day of the year.

Read about it on Bad Astronomy [Approaching the Sun].

You're On Notice

From The Stephen Colbert "On Notice Board" Generator. (Bears should also be on the list but I didn't have room.)

A Prayer for Appeasers

Greg Laden posted a A Boxing Day Prayer for all those who are afraid to speak out aganst supersition. I reproduce it below the fold but you need to read the complete article that goes with it on Greg's blog.

A Prayer to the Faith Based

I’m sorry, and I don’t mean to offend you,
And you didn’t even ask for this but
I’m going to put in a plug for your beliefs
So that you won’t get too mad at me as I utter words
With which you or someone you know may not agree,
(No matter how utterly wrong you may happen to be)

It is good that you are religious
And I will personally defend your right to believe
Whatever it is you do in fact believe,
And I affirm that it is OK to put
Phrases regarding your beliefs on my money
And for you to assume that
I will swear to your god

when I am on jury duty
when I am drafted into the army
when I am elected to office
when I am in the witness stand
and whenever else I must affirm
that I am moral and will not lie.

i Will Capitalize Your Word for God
And the Name of Your Holy Book
And Other Entities and Documents
As You Dictate These Rules To me.

I offer this pandering to your particular beliefs,
regardless of what they may happen to be,
despite the fact that your cultural ancestors,
the mavens and leaders of one church or another,
burned at the stake or otherwise humiliated mine,
The early scientists and freethinkers,
I affirm this because I cannot at the moment
Remember where I put my spine.

Amen.

Nobel Laureates: Bergström, Samuelsson, and Vane

The Nobel Prize in Physiology or Medicine 1982.

"for their discoveries concerning prostaglandins and related biologically active substances"

Sune K. Bergström (1916-2004), Bengt I. Samuelsson (1934-), and John R. Vane (1927-2004) received the Nobel Prize for discovering prostaglandins and working out their structure. In additon, Vane discovered the role of aspirin in inhibiting prostaglandin synthesis.

Prostaglandins are homones that mediate pain, inflamation and swelling. They also control blood clotting and and arterial constriction. See Why You need Linoleate and tomorrow's articles ("Prostaglandin Synthesis", "How Painkillers Work") for more information.

Why You Need Linoleate

Polyunsaturated fatty acids (PUFAs) are long chain fatty acids with multiple double bonds. Monday's molecule was linoleate or cis, cis -Δ^9,12- octadecadienate. It's an 18-carbon fatty acid with double bonds at positions 9 and 12. PUFA's are essential components of many biochemical pathways. (Note that this fatty acid is a normal cis fatty acid and not a trans fatty acid.)

The standard route for synthesis of PUFAs requires specific enzymes that create the double bonds at fixed positions. These enzymes are called desaturases. Other enzymes can extend the fatty acid chain from 18 carbons (18 carbons are the longest chains made by the normal fatty acid synthesis pathway). These enzymes are called elongases.

The combination of various desaturases and elongases will result in the synthesis of a wide variety of complex polyunsaturated fatty acids. One of these, arachidonate, is the precursor for synthesis of many eicosanoids—a class of compounds that includes the hormones prostaglandins, leukotrienes, and thromboxane.

Arachidonate is made from linoleate.

The first step in the pathway is activation of linoleate by attaching a cofactor called coenzyme A. The result is linoleoyl CoA, which is then converted to arachidonoyl CoA by the action of two desaturases and an elongase.


Now, here's the catch. Most eukaryotes contain a variety of desaturases that can create double bonds as far as 15 carbons away from the the carboxyl end of a fatty acid (i.e., at position 15). Mammals have lost some of these desaturase enzymes so they can't make any PUFA with a double bond beyond position 9. They (we) can't make linoleate even though it is absolutely required for life. We need to get it from our diet.

Tomorrow we'll learn how arachidonoyl-CoA is converted to prostaglandins and how aspirin, ibuprofen, acetaminophen, and other NSAIDS block the synthesis.

Shelley Batts in Toronto on New Years Eve

Shelley Batts of Restrospectacle describes her Toronto New Years and a Sad Rose Bowl. Apparently it went pretty good except that she couldn't get a cab at 3:30 am on Sunday night/Monday morning and she didn't like the Rose Bowl game.

Shelley, I can't do anything about the Rose Bowl but next time you need a cab in Toronto give me a call.

Edge Question for 2007

John Brockman runs an interesting "blog" called the Edge. He has assembled a cadre of intellectuals, and people who aspire to be intellectuals. Most of them are authors and Brockman is their agent.

This year's question is ...

The Edge Annual Question — 2007
WHAT ARE YOU OPTIMISTIC ABOUT? WHY?

As an activity, as a state of mind, science is fundamentally optimistic. Science figures out how things work and thus can make them work better. Much of the news is either good news or news that can be made good, thanks to ever deepening knowledge and ever more efficient and powerful tools and techniques. Science, on its frontiers, poses more and ever better questions, ever better put.

What are you optimistic about? Why? Surprise us!

The results are fascinating [THE WORLD'S LEADING THINKERS SEE GOOD NEWS AHEAD]. I haven't picked a favorite 'cause there are so many good ones. Many of them focus on issues that we have been discussing here: issues such as the fight between rationalism and superstition, the meaning of science, and science education.

Do you have a favorite?

Why European Countries Don't Have the Death Penalty

The recent discussion of capital punishment in another thread prompted me to look for opinion polls to see what kind of support for the death penalty there was in Europe and Canada. It turns out that a majority of citizens in those countries actually favor the death penalty in spite of the fact that their governments have abolished it.

Death penalty proponents make a big deal of this contrast. They claim that European societies are just as barbaric as American societies—although they don't actually put it in those words.

Are you interested to know how some American websites interpret this result? If so, read on, but before clicking on the "Read more" link I want to warn all Europeans that you may not like what you read. If you have high blood pressure you'd better skip it.

Here's an explanation written by Wesley Lowe on the Pro Death Penalty Webpage. Remember, he's trying to explain why European governments have abolished the death penalty in spite of the fact that a majority of Europeans support it.

Differences between European parliamentary government and the American separation-of-powers system also play a role. Parliamentary government may provide voters with more ideological variety, but it is much more resistant to political newcomers and fresh ideals which may support different political views. In parliamentary systems, people tend to vote for parties, not individuals; and party committees choose which candidates stand for election. As a result, parties are less influenced by the will of the people. In countries like Britain and France, so long as elite opinion remains sufficiently united (which, in the case of the death penalty, it has), public support cannot translate into legislative action. Since American candidates are largely independent and self-selected, they serve as a much more direct conduit between public opinion and actual political action.

Basically, then, Europe doesn't have the death penalty because its political systems are less democratic, or at least more insulated from public opinion, than the U.S. government.

This is so astonishingly ignorant that it leaves me speechless. Let's hear from other Americans on this point. Do you really believe that the government of the USA is more democratic and more open to fresh ideas than governments in Europe? Do you really believe that the US Congress is more responsive to public opinion than governments that have a parliamentary system? (While replying, keep in mind the frequency with which incumbent American politicians are turfed out of office. Contrast this with parliamentary systems where it's not uncommon for 50% of the seats to change hands in a general election.)

Brits Losing After American Invasion

According to recent reports red squirrels in Britain are facing extinction. There may be only 30,000 left in England, 10,000 in Wales, 10,000 in Northern Ireland, and 121,000 in Scotland [Red Squirrel Facts]. The European Red squirrels (Sciurus vulgaris) are being out-competed by American or Eastern gray squirrels (Sciurus carolinensis) introduced into Great Britain in 1876.

Human Brits are banding together to help the red squirrels fight off the foreign invasion [Friends of the Red Squirrel] but the prospects are dim. It looks like curtains for the reds.

This clearly has something to do with evolution. When one species out competes another and drives it to extinction we think of this as part of the process of evolution. But which process is it? It doesn't really count as natural selection, strictly defined, since that process involves differential success of individuals within a population. What do we call it when two species go head-to-head and only one survives?

Monday's Molecule #7

Name this molecule. The common name will do but there will be bonus points for finding the correct scientific name. This compound is essential in human diets. You will die if you don't get it in your food. Comments will be blocked for 24 hours. You can post your answer in the comments.