Fairy Rings

 
I look at the botany photo of the day every day. This is a service provided by the Botanical Gardens at the University of British Columbia and I really appreciate their attempt to wean us away from animals.

Usually the photographs are spectacular closeup images taken with cameras that are much more expensive than mine. But yesteday's picture was from Google Earth! It shows 100 year old fairy rings near Kensington Palace in central London. The rings are probably caused by Marasmius oreades. Find out how a little fungus can make rings visible from so high.

Innocent Man Released from Jail

 
Mahmoud Jaballah is called a "terrorism suspect." He has been in jail for five years but he's never been found guilty of anything. That means he's an innocent man according to my sense of justice and he'll remain innocent until proven guilty.

Yesterday he learned that he will soon be released. Today's Toronto Star has the story [Terror suspect ordered freed].

Toronto terrorism suspect Mahmoud Jaballah will be released on strict bail conditions after more than five years in jail without charges, despite government protests he remains a danger to Canada.

His release comes on the heels of last month's Supreme Court ruling that struck down an immigration law as unconstitutional and deals another blow to the government's handling of security cases involving non-citizens.

Yeast Mitochondria

 
There's a paper in this month's issue of Developmental Cell that uses the technique of electron tomography to examine the fine structure of a yeast cell. This technique involves slicing the cell into many thin sections then taking electron micrographs of each section and reconstructing a three-dimensional model of the cell.

The species is the fission yeast Schizosaccharomyces pombe and the results are spectacular. The image on the left was part of the Bio News Net press release.

The emphasis in the paper is on the organization of microtubules. Those are the thin green lines runing down the length of the cell. It turns out that many of the vesicles and mitochondria are associated with these microtubules. Here's the abstract of the paper ..

Polarized cells, such as neuronal, epithelial, and fungal cells, all display a specialized organization of their microtubules (MTs). The interphase MT cytoskeleton of the rod-shaped fission yeast, Schizosaccharomyces pombe, has been extensively described by fluorescence microscopy. Here, we describe a large-scale, electron tomography investigation of S. pombe, including a 3D reconstruction of a complete eukaryotic cell volume at sufficient resolution to show both how many MTs there are in a bundle and their detailed architecture. Most cytoplasmic MTs are open at one end and capped at the other, providing evidence about their polarity. Electron-dense bridges between the MTs themselves and between MTs and the nuclear envelope were frequently observed. Finally, we have investigated structure/function relationships between MTs and both mitochondria and vesicles. Our analysis shows that electron tomography of well-preserved cells is ideally suited for describing fine ultrastructural details that were not visible with previous techniques.

One of the most interesting things about this paper is that it illustrates the structure of mitochondria. Look at the picture on the right from their paper. The gold things are mitochondria and they appear to be stuck to microtubules. Individual mitochondria are shown in the inserts in order to illustrate the convoluted and branching structures of those that are associated with microtubules. (The one labelled "G" is not stuck to microtubules.)

Most people don't realize that mitochondria are so complicated. Furthermore, the structures are dynamic—they can change significantly in the space of minutes.

Höög, J.L., Schwartz, C., Noon, A.T., O'Toole, E.T., Mastronarde, D.N., McIntosh, J.R., and Antony, C. (2007) Organization of Interphase Microtubules in Fission Yeast Analyzed by Electron Tomography. Developmental Cell 12: 349-361.

James Randi and Richard Dawkins

 
It's a shame when you get two smart people like this on the same stage and all you get are banalities. The audience must have been very disappointed.

Nobel Laureate: Paul Hermann Müller

 
The Nobel Prize in Physiology or Medicine 1948.

"for his discovery of the high efficiency of DDT as a contact poison against several arthropods"


Paul Hermann Müller won the Nobel Prize in 1948 for is discovery that DDT was an effective insect poison [see Monday's Molecule #16 and DDT Blocks the Voltage-Gated Sodium Channel]. Müller was looking for a contact poison that would protect plants from insects. He extended the work of others who discovered compounds that could be applied to wool to prevent them from being ruined by moths. These compounds resembled DDT but they were not as effective. Müller's approach is described in the presentation speech ...

Paul Müller went his own way and tried to find insecticides for plant protection. In so doing he arrived at the conclusion that for this purpose a contact insecticide was best suited.

Systematically he tried hundreds of synthesized organic substances on flies in a type of Peet-Grady chamber. An article by the Englishmen Chattaway and Muir, gave him the idea of testing combinations with the CCl3 groups, and this then finally led to the realization that dichloro-diphenyl-trichloro-methylmethane acted as a contact insecticide on Colorado beetles, flies and many other insect species under test. He determined its extraordinary persistence, and simultaneously developed the various methods of application such as solutions, emulsions and dusts.

In trials under natural conditions Müller was able to confirm the long persistent contact action on flies, Colorado beetles and gnats (Culex).

Subsequent work revealed that DDT was effective against a wide variety of insects and was harmless to mammals. Among the insects that were killed by DDT were lice, the carriers of thyphoid, and malaria mosquitos.

At the time, Müller was working for the J.R. Geigy Dye-Factory Co. in Basel Switzerland and he had given samples of DDT to the Swiss Army for testing. The results demonstrated that insect borne diseases could be controlled by DDT.

At that time, the Allied Armies of the West were struggling with severe medical problems. A series of diseases transmittable by insects, diseases such as typhus, malaria and sandfly fever claimed a large number of victims and interfered with the conduct of the War. The Swiss, who had recognized the great importance of DDT, secretly shipped a small quantity of the material to the United States; in December of 1942 the American Research Council for Insectology in Orlando (Florida) undertook a large series of trials which fully confirmed the Swiss findings. The war situation demanded speedy action. DDT was manufactured on a vast scale whilst a series of experiments determined methods of application. Particularly energetic was General Fox, Physician-in-Chief to the American forces.

In October of 1943 a heavy outbreak of typhus occurred in Naples and the customary relief measures proved totally inadequate. General Fox thereupon introduced DDT treatment with total exclusion of the old, slow methods of treatment. As a result, 1,300,000 people were treated in January 1944 and in a period of three weeks the typhus epidemic was completely mastered. Thus, for the first time in history a typhus outbreak was brought under control in winter. DDT had passed its ordeal by fire with flying colours.

By the late 1950's it became apparent that extensive use of DDT to control insects leads to its accumulation in the environment. This, in turn, leads to its concentration in the tissues of some animals, such as fish. The long term build up of DDT causes illness and death and it was finally banned in most countries in the 1970's.

Alcoholics Anonymous: 12 Steps

 
This month's reader's Digest has a couple of articles on Alcoholics Anonymous. The gist of the articles is that the famous 12 steps really don't work all that well. Apparently, there's no data to support the claim that Alcoholics Anonymous is successful at getting people to stop drinking.

I had no idea what these 12 steps were until they were published in the articles I read yesterday. For those of you who don't know, here they are [Alcoholics Anonymous]. I'm not surprised that this isn't a magic bullet but I am surprised at how religious AA must be. They must think that most alcoholics are Christians.

THE TWELVE STEPS
OF ALCOHOLICS ANONYMOUS

1. We admitted we were powerless over alcohol ﾗ that our lives had become unmanageable.
2. Came to believe that a Power greater than ourselves could restore us to sanity.
3. Made a decision to turn our will and our lives over to the care of God as we understood Him.
4. Made a searching and fearless moral inventory of ourselves.
5. Admitted to God, to ourselves and to another human being the exact nature of our wrongs.
6. Were entirely ready to have God remove all these defects of character.
7. Humbly asked Him to remove our shortcomings.
8. Made a list of all persons we had harmed and became willing to make amends to them all.
9. Made direct amends to such people wherever possible, except when to do so would injure them or others.
10. Continued to take personal inventory and when we were wrong promptly admitted it.
11. Sought through prayer and meditation to improve our conscious contact with God, as we understood Him, praying only for knowledge of His will for us and the power to carry that out.
12. Having had a spiritual awakening as the result of these steps, we tried to carry this message to alcoholics, and to practice these principles in all our affairs.

Atheists: Get Out of the USA!

 
From my [confined] space comes this copy of a letter to the editor. I don't know which paper it appeared in.

Let me know if I can help out. I can arrange temporary residence in Canada and help you find a good job. I'll teach you how to speak Canadian and how to go about cancelling your health insurance. I can even put you in touch with someone who will buy all your guns.

I'll even treat you a curling broom and a Toronto Maple Leafs sweater to help you get adjusted as quickly as possible. Do you like poutine?

DDT Blocks the Voltage-Gated Sodium Channel

 
Monday's Molecule #16 is 1,1,1-trichloro-2,2 bis(p-chlorophenyl) ethane, better known as DDT. DDT is a powerful insecticide. It binds to the voltage-gated sodium channel and locks it in the open state. Prolonged influx of sodium ions causes the nerves to fire repeatedly and this causes death of the insect.

The reason DDT is so powerful is due to its specificity. It binds to insect channel proteins but not to those of other animals (or plants, fungi, protists, and bacteria). Thus, it is an effective insecticide used to fight malaria and other insect borne diseases.

Unfortunately, even though DDT is not immediatly toxic to other animals it does have one disadvantage: it is extremely stable—its biological half-life is about eight years. Furthermore, DDT is stored in fatty tissues and its buildup in birds and fish resulted in considerable loss of these species. That, coupled with the evolution of DDT resistant insects, led to a ban of DDT in most countries by the 1970's.

Rachel Carson is largely credited with launching the environmental movement in 1962 with the publication of Silent Spring. The title refers to a world without birds. While I was writing this up I did a quick survey of the graduate students in the nearby labs and none of them had ever heard of Rachel Carson. Not only that, neither had several of my colleagues. I feel old.

One of the main targets of Silent Spring was DDT. By the time the book was published it was estimated that DDT had saved the lives of millions of people through prevention of malaria and thyphoid but it's effectiveness was much diminished. That's why the ban was not as controversial as it might have been.

Let's look at the biochemistry of DDT. We have already learned about the simple voltage-gated potassium channel. The Na⁺ (sodium) channel is closely related to the K⁺ channel protein. Recall that the K⁺ channel consists of four identical subunits surrounding a central hole through which K⁺ ions enter the cell.

The Na⁺ channel protein is much larger than the K⁺ channel subunit because it consists of four of the smaller subunits fused into a single polypeptide chain. The tolopology of the Na⁺ channel protein is shown below.

Each of the domains (I-IV) corresponds to a single subunit of the K⁺ channel. Like the K⁺ channel, the four domains of the Na⁺ channel protein are arranged around a central tunnel through which sodium ions enter the cell. The S5 and S6 helices line the tunnel.

The toplogy diagram above shows the locations of mutations conferring resistance to DDT and similar drugs. Each one represents mutants identified in resistant houseflies, fruit flies, mosquitos, or moths. The important mutations are substitutions at the 932 position normally occupied by leucine (L932) and at the 929 position normally occupied by threonine (T929) (blue dots). For example, the substition of isoleucine for threonine at 929 (T929I) confers almost complete resistance to DDT.

Incidently, the methionine at 918 (M918) is what confers sensitivity to DDT in the insect voltage-gated Na⁺ channel. Other animlas have a different amino acid at this position and they are not sensitive to DDT.

O'Reilly et al. (2006) modeled the structure of the Na⁺ channel using the known structures of the K⁺ channel proteins. This is necessary because the Na⁺ channel has not been crystallized. It's an excellent way to get a structure when you know that two proteins are homologous (descended from a common ancestor).

From the model, the authors were able to focus on the probable site of DDT binding based on the known mutations to resistance. In this case, they looked at the interface between helix S5 in Domain II and nearby helices S6 from Domain II (IIS6) and S6 from Domain III (IIIS6), which packs against IIS5 in the structure. They tried docking various insecticides in this region and came up with a good fit in all cases. The DDT binding site is shown below.

Note that the side chains of T929 and L932 interact directly with DDT. These are the sites of mutations to high levels of resistance. It looks like changes to these amino acids prevent binding of DDT and that's the basis of resistance.

The S4-S5 linker helix is shown in yellow in this figure. Recall that this is the helix that responds to membrane potential by reorienting to a more vertical position. This, in turn, shifts the S5 and S6 helices to more vertical postions and closes the channel. In the presence of DDT the S5 and S6 helices are effectively cross-linked and they cannot shift to a position where they move closer together. This prevents closing of the channel. DDT locks the channel in the open conformation leading to a continual influx of Na⁺, uncontrolled firing of the nerve, and eventual death.

O'Reilly, Andrias O., Khambay, Bhupinder P. S., Williamson, Martin S., Field, Linda M., Wallace, B. A., and Davies, T. G. Emyr (2006) Modelling insecticide-binding sites in the voltage-gated sodium channel. Biochem. J. (2006) 396:255–263.

Joni Mitchell Sings About DDT

 
Here's part of the lyrics from Big Yellow Taxi. I don't know about the rest of you but I'd much rather watch and listen to Joni Mitchell than Al Gore or David Suzuki. You may not recognize the song until you hear her sing it.

They took all the trees
Put 'em in a tree museum
And they charged the people
A dollar and a half just to see 'em

Don't it always seem to go
That you don't know what you've got
Till it's gone
They paved paradise
And put up a parking lot

Hey farmer farmer
Put away that DDT now
Give me spots on my apples
But leave me the birds and the bees
Please!

Voltage-Gated Ion Channels

 
Cells have to import and export ions in order to survive. Since ions are charged molecules, they do not pass through the cell membrane. This means they have to be transported by proteins that are embedded in the membrane.

There are many different kinds of transporters. Some of them use up energy to move ions across the membrane by a process called active transport. Some of them simply open a channel and allow ions to pass through. Let's look at some channel proteins.

A typical channel protein consists of several subunits arranged around a central hole that permits passage of ions. In this case we'll be dealing with ion channel proteins that allow movement of Na⁺ (sodium) or K⁺ (potassium) ions from the outside of the cell (top) to the cytoplasm (bottom). The part of the protein that spans the membrane is usually an α helical region. In fact, there are usually several α helices in a channel protein.

The flow of ions must be regulated, so these channel proteins must be capable of opening and closing to allow or restrict the flow of Na⁺ or K⁺. This is why they're called gated channels. There are several ways of controlling the gate. We are going to be discussing mechanisms that respond to the membrane potential—the difference in charge on either side of the membrane. For example, the wave of membrane depolarization that occurs as a nerve impulse, or action potential, moves along the axon of a nerve cell.

These channel proteins are called voltage-gated ion channels.

The simplest kind of voltage-gated ion channels are the K⁺ (potassium) channels found in bacteria and in eukaryotes. The role of potassium channels is to allow influx of potassium if the concentration inside the cell drops below some minimal value. Normally the concentration of K⁺ in the cytoplasm is about 100 times greater than the concentration outside the cell because K⁺ ions are actively transported into the cell as Na⁺ ions are pumped out. The concentration of Na⁺ outside the cell is about 10 times higher than the inside concentration.

From time to time, these concentrations are perturbed (e.g., during the firing of a nerve impulse) and the sodium and potassium channels will open to restore the resting state concentrations. The gates in the ion channels will only open for 1 millisecond but this is enough to allow entry of thousands of ions per channel.

The structures of several bacterial K⁺ channels are known and recently the structure of the homologous channel from rat was solved. The structures are very similar. Let's look at the rat voltage-gated K⁺ channel (Longe et al. 2005a; Long et al. 2005b).

The complete channel consists of four identical subunits colored red, green, yellow, and blue in the figure on the left. The crystallized protein has an additional β subunit at the bottom attached to the T1 cytoplasmic domain but I've removed it in order to simplify the description. The β subunit contains an oxidoreductase activity that's coupled to the influx of potassium.

If you look at the structure of the single red subunit you can see that it consists of a bundle of four transmembrane α helices labelled S1-S4 on the left and two others (S5 and S6) on the top right. The S5 and S6 helices are the ones that form the central channel when the four subunits come together. This is most easily seen in the top view at the bottom of the figure. The black dot in the middle represent a K⁺ ion about to pass through the channel.

The structure shown is the open conformation that allows passage of ions. The closed conformation was modeled from the known structure of the bacterial channels and experimental data that implicated the S4-S5 linker helix in the gating process. You can see this linker helix in the figure above. It joins the S1-S4 bundle to the S5, S6 bundle. It is not one of the transmembrane helices. The results are shown below.

In the closed conformation, the S4-S5 helix responds to changes in the membrane potential by twisting from a horizontal position to a slightly more vertical position. This causes the S5 and S6 transmembrane helices to also adopt a more vertical orientation. Since the same conformational change occurs in all four subunits, the net effect is to make the entire protein more narrow and this closes the channel in the middle of the protein. The switch between the open and closed conformations is extremely rapid and it is very sensitive to changes in the membrane potential.

Long, Stephen B., Campbell, Ernest B., MacKinnon, Roderick (2005a) Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel. Science 309:897-903.

Long, Stephen B., Campbell, Ernest B., MacKinnon, Roderick (2005b) Voltage Sensor of Kv1.2: Structural Basis of Electromechanical Coupling. Science 309:903-908.

Ann Coulter Finally Gets Something Right

 
A Gentleman's C (love that title!) quotes Ann Coulter from her book Godless,

...Professors are the most cosseted, pussified, subsidized group of people in the U.S. workforce. They have concocted a system to preemptively protect themselves for not doing their jobs, known as "tenure." They make a lot of money, have health plans that would make New York City municipal workers' jaws drop, and work -- at most -- fifteen hours a week.

At last she gets something right ... or almost right. Well ... maybe a little bit right.

Tenure doesn't protect us from not doing our jobs, it protects us when we're doing our jobs. If you don't do your job you're going to lose it and tenure won't, and shouldn't, protect you. Tenure means that if Ann Coulter were a Professor she couldn't be fired for being such an ass, as long as she works hard at it. But that's a minor difference. For Ann Coulter, being 180° wrong is close enough.

Some Professors make a lot of money, but only when they get old. Most Professors make far less than they could if they were in the private sector. Some make less than a high school teacher. But that's a minor discrepancy. Ann Coulter is probably not familiar with how the real world lives.

Canadian Professors have a good health plan. But that's not very special since all Canadians have a good health plan. It's one of the benefits of living in a civilized society. Ann Coulter ought to try it sometime. Maybe she should move to Great Britain or Australia. They are pro-war staunch American allies. She'd like it there.

As for workload, I checked with my colleagues and they all agree that 15 hours a day is too much. The average seems to be closer to 10-11 hours a day during the week and another 10 or so hours on the weekend. The total comes out to about 60 hours. In this case Ann was being too generous. Professors put in a lot of hours but 15 hours per day is not sustainable over the long haul.

[Hat Tip: John Lynch]

Joni Mitchell Inducted into the Canadian Songwriters Hall of Fame

 
Joni Mitchell was born in Fort Macleod, Alberta but moved to Saskatoon, Saskatchewan at a young age. She's really a Saskatchewan girl.

Famous not only as a singer-songwriter but also as an artist, she was inducted into the Canadian Songwriters Hall of Fame on January 28, 2007 at the Toronto Convention Centre Gala. The performances, including James Taylor singing Woodstock, were just broadcast this evening on CBC.

Here's Joni singing one of her most famous songs Both Sides, Now also known as Clouds. Look below the fold to see her singing Woodstock. Here's a link to Chelsea Morning [lyrics], one of her signature songs. They just don't write 'em like that any more.

By the time we got to Woodstock
We were half a million strong
And everywhere there was song and celebration
And I dreamed I saw the bombers
Riding shotgun in the sky
And they were turning into butterflies
Above our nation

We are stardust
Billion year old carbon
We are golden
Caught in the devil's bargain
And we've got to get ourselves
back to the garden

Centre for Inquiry

 
Visit the Centre for Inquiry, Ontario. The new facility is just two blocks south of the main University of Toronto campus, and just a short walk from my office.

The grand opening is this Saturday night. I know you've got nothing better to do on Saturday night (the Brier semi-finals are in the afternoon) so come on out and help them get the ball rolling.

Don't forget to keep Thursday, March 22nd free for "God and Evolution."

God and Evolution

 
This is in my building. I'm going. Email me if you want to meet for dinner before it starts. (That includes you, Denyse. I'm buying!)

Brian Alters

Dan Brooks

The Oprah Winfrey Leadership Academy for Girls

 
I watched the TV show [ABC Special] on the The Oprah Winfrey Leadership Academy for Girls in South Africa. It's very impressive. I'm certain that by educating the best and the brightest girls in South Africa (and perhaps all of Africa) Oprah is doing more to ensure the future of Africa than most others. The empowerment of women in Africa was a constant theme in the speeches of Stephen Lewis. I'm sure he's right and Oprah is helping. You can't help but be impressed by these young girls.

But this is the same Oprah Winfrey that fell hook line and sinker for "The Secret" [Oprah Winfrey Has a Secret]; a point that PZ Myers returns to today in Shame on Oprah. An article on Salon [Oprah's ugly secret] makes the same point. (PZ's comments are based on the Salon article.)

Here's some of the things Peter Birkenhead says in the Salon article.

Oprah's TV special about the Leadership Academy, essentially an hourlong infomercial, was just as well-coiffed and "visuals"-heavy. In fact, when Oprah was choosing her students, her important criteria must have included their television interview skills. On-camera interviews with the girls were the centerpiece of the special, but as one spunky, telegenic candidate after another beamed her smile at the camera, I couldn't help wondering how Joyce Carol Oates or Gertrude Stein or Madame Curie would have fared -- would they have "shined" and "glowed," or more likely talked in non-sound-bite-friendly paragraphs and maybe even, God forbid, the sometimes "dark" tones of authentic people, and been rejected. Sadly, the girls themselves (and who can blame them, desperate 12-year-olds trying to flatter their potential benefactor) parroted banal Oprah-isms, like "I want to be the best me I can be," and "Be a leader not a follower" and "Don't blend in, blend out," with smiley gusto.

When the special was over, I found myself equally impressed and queasy, one part hopeful, one part worried. I was happy the school was there, but disturbed by the way it created an instant upper class out of the students, in a country that doesn't exactly need any more segregation into haves and have-nots. I was hopeful for the students but nervous about what, exactly, they will be taught in a place called the Oprah Winfrey Leadership Academy. Will it be more "best me I can be" bromides? Will "The Secret" be on the syllabus? Oprah herself is going to teach "leadership classes" at the school, after all.

Has Oprah ever done anything that didn't leave people with mixed feelings?

Good point. The answer is yes, and no. I don't have any mixed feelings about her descent into superstitious nonsense and her gullibility when it comes to being duped by modern snake-oil salesmen. She's just plain wrong about "The Secret" and that other nonsense, and her popularity is hurting the cause of rationalism.

On the other hand, I really admire what she's trying to do in South Africa in spite of the "elitist" criticism. I'm not afraid of elitism when it's based on merit and achievement. But that admiration is tempered by the mixed feelings that Peter Birkenhead refers to. I wish there was another rich woman who felt passionately about educating black girls in Africa but who didn't come with Oprah's baggage.

I never thought about the kind of girls Oprah is selecting. I wonder about a 12 year old Gertrude Stein, or even a young Madeleine Albright. Would Jane Goodall have made the cut? What about Jane Fonda—would she have been picked? or Anne Frank?

There's no doubt that Oprah's doing a lot of good with her South African project, and with many other charitable works. And yeah, I know, her book club "gets people to read," and yadda yadda yadda. But there's also no doubt that a lot of us have been making forgiving disclaimers like that about Oprah for years. And that maybe they amount to trains-running-on-time arguments. Maybe it's time to stop. After reading "The Secret," it seemed to me that there were basically three possibilities: 1) Oprah really believes this stuff, and we should be very worried about her opening a school for anyone. 2) Oprah doesn't believe this stuff and we should be very, very worried about her opening a school for anyone. 3) Oprah doesn't know that any of this stuff is in the book or on her Web site and in a perfect world she wouldn't be allowed to open a school for anyone.

The things that Oprah does, like promoting "The Secret," can seem deceptively trivial, but it's precisely because they're silly that we should be concerned about their promotion by someone who is deadly earnest and deeply trusted by millions of people. It's important to start taking a look at Oprah because her philosophy has in many ways become the dominant one in our culture, even for people who would never consider themselves disciples. Somebody is buying enough copies of "The Secret" to make it No. 1 on the Amazon bestseller list. Those somebodies may be religious zealots or atheists, Republicans or Democrats, but they are all believers, to one degree or another, and, perhaps unwittingly, in aspects of the Oprah/"Secret" culture. And yes, sure, a lot of the believing they do is harmless fun -- everybody's got some kind of rabbit's foot in his pocket -- but we're not talking about rabbits' feet here, we're talking about whole, live rabbits pulled out of hats, and an audience that doesn't think it's being tricked.

This is a tough one. In an ideal world we would like to think that Oprah would come to her senses and realize that her personal philosophy is flawed. We would like to believe that she can change her mind and become rational. Then we would have the best of both worlds—a rich rational woman who is willing to spend her fortune to improve the world.

It ain't gonna happen, is it? At some point we need to make a choice. I'm hoping that the school will be taken over by more rational people when Oprah loses interest. I'm hoping that those bright young girls are too smart to fall for the pseudo-intellectual nonsense of "The Secret" (or religion, for that matter). Maybe they're a lot smarter than the women who show up for the taping of the Oprah Winfrey Show in Chicago. Wouldn't that be wonderful? How delicious it would be if five years from now a bevy of graduates from the Oprah Winfrey Leadership Academy were to denouce "The Secret"!

Here's the bottom line. It's scary when you put it like this.

Not that any of this is new. Aimee Semple McPherson, "The Power of Positive Thinking," Father Coughlin, est, James Van Praagh -- pick your influential snake-oil salesman or snake oil. They were all cut from the same cloth as Oprah and "The Secret." The big, big difference is, well, the bigness. The infinitely bigger reach of the Oprah empire and its emissaries. They make their predecessors look like kids with lemonade stands. It would be stupidly dangerous to dismiss Oprah and "The Secret" as silly, or ultimately meaningless. They're reaching more people than Harry Potter, for God-force's sake. That's why what Oprah does matters, and stinks. If you reach more people than Bill O'Reilly, if you have better name recognition than Nelson Mandela, if the books you endorse sell more than Stephen King's, you should take some responsibility for your effect on the culture. The most powerful woman in the world is taking advantage of people who are desperate for meaning, by passionately championing a product that mocks the very idea of a meaningful life.

That means something.