Rx: Reductionist vs. pluralist views of Cancer

CancercellCancer, the malignant evil that corrodes fatally, is supposed to start in one cell. In appearance and behavior, this cell and its daughters are so different from their “normal” predecessors and counterparts that they appear to represent a new species. In this essay, I suggest that the transformation of a non-malignant cell into a frankly malignant state accompanied by all the biologic changes that define cancer as a disease (expansion, angiogenesis, metastasis) may follow the rules of evolutionary biology during speciation. In the strictest sense, speciation refers to reproductive isolation, which is obviously not the case here; subsequently I will use “clones” of cells in lieu of species. How this clone develops a growth advantage over its surrounding neighbors and at the same time, manages to suppress the growth of its normal counterparts, is a subject which is not well understood. The conventional approach of most scientists to such a problem is that of reductionism where an attempt is made to break the cell down into its individual components, and concentrate on identifying abnormalities that could explain the malignant characteristics. Reductionists would view the initiation and subsequent expansion of a cancer cell into an overwhelming clone as being driven by events related predominantly to the cell itself; for example the dysregulation of genes by mutations or deletions. Although, the reductionist method constitutes the backbone of solid science, transformation of a normal cell into a frankly malignant one is a gradual process involving multiple steps, making it difficult to apply the reductionist approach to the problem. These steps are not confined to the cell alone, but also involve a dynamic microenvironment which affects, and is in turn, affected by the expanding population of the abnormal cells. Thus the cell and its microenvironment, or the seed and the soil, constitute a complex system, and pluralists would argue that complex systems cannot be reduced to simple properties of their individual components. Or, to paraphrase Einstein, one can reduce the problem to its simplest possible solution, but no simpler.

Thousands of putative cancer cells are produced in the body each day, but die without further expansion because they are not well equipped to survive in an environment optimized for the support of normal cells. An ongoing interaction between a potential cancer cell and its micro-environment is therefore a necessary requirement for their co-evolution towards a malignant disease state. In other words, even as thousands of cancer cells are produced in the body on an annual basis, the clinical disease with all its malignant manifestations does not appear unless the cancer cell has had a chance to “evolve”. In fact, the situation has many parallels with the ongoing lively debate between the two groups of evolutionary biologists regarding speciation. The orthodox Neo-Darwinians (Maynard Smith, Richard Dawkins, Daniel Dennett) are reductionists who believe that natural selection is the sole engine driving evolution. The proponents of the punctuated equilibrium hypothesis (Niles Eldridge, (the late) Stephen J. Gould and Richard Lewontin) see evolution as being more complex so that natural selection may be the primary but not the exclusive source of modification. They are the pluralists. Application of the broad principles of evolutionary biology to carcinogenesis may define the sequence of events involved in the development of a malignancy, thereby locating therapeutic targets where intervention is likely to lead to an arrest, if not a reversal, of the process.

Let us take the example of the human bone marrow which is an exceedingly dynamic compartment with billions of cells of many different varieties being produced, as well as being programmed to die on an hourly basis. Deviancy is not well tolerated in this high throughput factory. Darwinian tenet would hold that natural selection acts to maintain stasis in a population by jettisoning the anomalous. Survival of a potential cancer cell is clearly incongruous in this background, since it should have been weeded out long before its daughters were able to overwhelm the marrow, but not if the initiation of cancer is a serendipitous phenomenon. Within every population, there are cells with minor variations; some cells are more “fit” to survive than others. Cellular proliferation in the bone marrow, occurs in “niches” where the balance between the negative and positive growth signals is tilted towards the latter. Imagine that a population of cells happened to become isolated in a microenvironmental niche that provided less than ideal support (for example, a slightly hypoxic environment) for the growth of normal cells. Some of the trapped cells may have been better able to survive in this abnormal environment as compared to normal cells that would have died perhaps because they were smaller in size, or they divided faster, or could withstand hypoxia better or lacked a surface protein necessary for recognition by a death effector for elimination. In short, cancer cells may be able to survive and outnumber normal cells in certain “abnormal” microenvironments precisely because of their inability to compete with normal cells in the “normal” microenvironment. The abnormality is best manifested as a growth advantage. If a cancer cell enjoys even a slight growth advantage, it will outnumber its normal counterparts within a few generations, something that can happen in a matter of weeks or days as far as the human body is concerned.

I would like to posit that at least in some instances, the initiation of cancer involves isolation and entrapment of variant cells in a microenvironmental milieu that is not conducive to the proliferation of normal cells. Any variation that enhances the likelihood for survival and reproduction will then be passed from one generation to the next simply as a result of natural selection. Accumulation of even subtle genetic changes over many generations could eventually have a dramatic effect.

An example is that of fatty foods causing gastrointestinal cancer. In rather simplistic terms, there is a burst of secretion of bile acids in the gut following the ingestion of a fatty meal. These bile acids perform their metabolic function efficiently, but as a side effect, also induce programmed cell death in the surrounding mucosal cells. With frequent fatty meals and repetition of this cycle, the stressed cells facing the bile acid assaults fight back by developing survival strategies in this noxious environment. Eventually, one cell will either be selected for survival because of its “differential fitness” or because it has silenced the genes that mediate programmed cell death. An epigenetic mechanisms that cancer cells have been widely shown to employ for silencing genes for death and differentiation is that of hyper-methylation. Simply by adding methyl groups to the cytosines (CpG islands) in the promoter sites of critical genes, the cell can block transcription of that gene. This cell develops the ability to thrive in a microenvironment which is killing its normal counterparts. A survival phenotype is a cancer phenotype.

Chance factors could operate to facilitate the survival of a variant clone of cells, slightly different than the normal cells, but it is still natural selection that does the rest of the work. The role of natural selection is to improve the “fit” between an organism and its environment. Expansion of the clone of cells must be accompanied by co-evolution of the seed (cells) and the soil (microenvironment). Take the following example. Cancer cells may proliferate continuously either because the soil is providing these “growth factors”, or the cell is constitutively turned “on” because of a genetic mutation. The cancer cell must not only divide and expand its own population continuously, it must also shut off the proliferation of normal cells. One way this is accomplished may be by developing the ability to proliferate in response to signals that are inhibitory to the normal cell as illustrated in the following example.

Cells communicate and transmit signals through proteins called cytokines. Tumor necrosis factor or TNF is a cytokine that induces normal cells to undergo programmed cell death. Some leukemia cells on the other hand are stimulated to proliferate by TNF. Let us go back to our statement that within every population, there are cells with minor variations; some cells are more “fit” to survive than others. Now imagine what happens when there are a number of stem cells with varying “fitness” trapped in a microenvironmental niche which had a higher than normal level of TNF. The “normal” cells will be inhibited from proliferating while the slightly “abnormal” one will begin to proliferate. With time, the more TNF is produced, the better the abnormal cell fits the environment and expands its population at the expense of its normal counterpart. In fact, the abnormal cell itself may start producing TNF to enhance its own growth while at the same time suppressing that of the normal cells.

The microenvironment of cancer cells in the body not only consists of stromal cells capable of producing cytokines such as TNFa, but in addition harbors components of the immune system as well as newly formed blood vessels which directly affect the growth and perpetuation of the abnormal clone of cells. An important implication of these biologic insights is that the “cause” of cancer as a disease entity is at least in part related to the changed microenvironment and not something restricted to the intrinsic properties of the cancer cell. Consequently, strategies directed at eliminating the malignant cell alone, no matter how efficient, will only solve part of the problem at best, and be successful temporarily. Even if 99% of the abnormal cancer cells are destroyed but the microenvironment is left intact with all its abnormal features, then normal cells would not be able to survive for long in that setting, resulting in the redistribution of the growth advantage back to a “more fit” or abnormal cell causing relapse. This scenario is unfortunately all too familiar in the treatment of most cancers. Chemotherapy can produce striking complete remissions, but the cancers relapse eventually, and the second time around, they are more resistant to therapy as the cells causing a relapse have followed the Darwinian selection process of having survived in the presence of the noxious drug in the first place. In order to obtain complete and durable responses, both the seed and the soil would need to be targeted.

Developing models like this is not just of theoretical interest, but there are immediate and practical applications of these to the human condition. The conclusion is that it should not be a case of “either/or” in terms of the reductionist versus pluralistic view of cancer, but a combination of the two views as far as planning effective treatment is concerned. In order to kill the seed or the cancer cell, a reductionist approach must be used to identify the key steps involved in the perpetuation of the clone. Targeted therapies should be developed to interfere with the specific intracellular steps, for example an abnormal protein being produced by a mutated gene. In addition, with the pluralistic view of cancer in mind, the extracellular components should be targeted simultaneously, for example blood vessels or cytokines such as TNF. The future success of cancer treatment will depend on how rapidly and how effectively we learn to combine therapies which simultaneously attack several targets in the cell as well as the microenvironment. Studying cancer cells in isolation without their natural in vivo microenvironment, or through artificial mouse models will only yield limited information.

In summary then, cancer initiation could be the result of the serendipitous presence of an abnormal cell in an abnormal microenvironmental niche. Natural selection then works to improve the fitness between the seed and the soil, making both increasingly abnormal. The rate at which this occurs depends at least in part on the body’s ability to mobilize the immune system to mount a counterattack, and that of the cells to expand their clone, for example through the formation of new blood vessels. Thus, the time from initiation to actual disease manifestation could vary considerably depending on the forces driving the fitness landscape. The famous quip by a Neo-Darwinist (who believe that evolution is a gradual process) criticizing the punctuated equilibrium theory that he “did not believe in evolution by jerks” was answered by the Gould group (who suggest that periods of stasis are punctuated by sudden proliferation of species) with the retort that they “did not believe in evolution by creeps”. The evolution of cancer is probably best described by both jerks and creeps.

Previous Rx Columns:
Spicing Cancer Treatment
The War on Cancer

Sunday, January 8, 2006

James Frey: The Man Who Conned Oprah

From The Smoking Gun:

FreytwotwotwoThree months ago, in what the talk show host termed a “radical departure,” Winfrey announced that “A Million Little Pieces,” author James Frey’s nonfiction memoir of his vomit-caked years as an alcoholic, drug addict, and criminal, was her latest selection for the world’s most powerful book club.

In an October 26 show entitled “The Man Who Kept Oprah Awake At Night,” Winfrey hailed Frey’s graphic and coarse book as “like nothing you’ve ever read before. Everybody at Harpo is reading it. When we were staying up late at night reading it, we’d come in the next morning saying, ‘What page are you on?'” In emotional filmed testimonials, employees of Winfrey’s Harpo Productions lauded the book as revelatory, with some choking back tears. When the camera then returned to a damp-eyed Winfrey, she said, “I’m crying ’cause these are all my Harpo family so, and we all loved the book so much.”

But a six-week investigation by The Smoking Gun reveals that there may be a lot less to love about Frey’s runaway hit, which has sold more than 3.5 million copies and, thanks to Winfrey, has sat atop The New York Times nonfiction paperback best seller list for the past 15 weeks.

More here.  [Thanks to Steven Anker.]

UPDATE: More on Frey here.

Can Bayesian reasoning help explain how the mind works?

In the Economist:

SCIENCE, being a human activity, is not immune to fashion. For example, one of the first mathematicians to study the subject of probability theory was an English clergyman called Thomas Bayes, who was born in 1702 and died in 1761. His ideas about the prediction of future events from one or two examples were popular for a while, and have never been fundamentally challenged. But they were eventually overwhelmed by those of the “frequentist” school, which developed the methods based on sampling from a large population that now dominate the field and are used to predict things as diverse as the outcomes of elections and preferences for chocolate bars.

Recently, however, Bayes’s ideas have made a comeback among computer scientists trying to design software with human-like intelligence. Bayesian reasoning now lies at the heart of leading internet search engines and automated “help wizards”. [Stanford Encyclopedia of Philosophy entry on Bayes’s Theorem.] That has prompted some psychologists to ask if the human brain itself might be a Bayesian-reasoning machine. They suggest that the Bayesian capacity to draw strong inferences from sparse data could be crucial to the way the mind perceives the world, plans actions, comprehends and learns language, reasons from correlation to causation, and even understands the goals and beliefs of other minds.

These researchers have conducted laboratory experiments that convince them they are on the right track, but only recently have they begun to look at whether the brain copes with everyday judgments in the real world in a Bayesian manner.

new artists: trecartin

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WHEN THE CHOICE BETWEEN lingering in front of a video projector or hitting a half-dozen other galleries is increasingly a cinch, the jolting energy, nerve, and intricacy of twenty-four-year-old Ryan Trecartin’s work in the medium comes as no small shock. An abiding interest in indie rock, goth, psychedelia, and other hot topics won’t distinguish his practice from that of other artists of his generation. But everything aesthetic about his videos—from the baroque screenplays that polish flippant teen slang into cascading soliloquies to the dueling fascinations with profound loneliness and extremely affected behavior to the swarming, jumbled, yet precisely composed shots that pack each frame to the rafters with visual stimuli—displays a near obliviousness to what’s going on in his field, whether it be the clichés of current video art or the signature styles of past experimental films. Trecartin does, however, share a penchant for full-frontal gayness and a love of extravagance with the movie directors his work most immediately brings to mind: Kenneth Anger, Jack Smith, and early John Waters.

more from Artforum here.

james wood on henry green

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To devotees of Henry Green, it seems extraordinary that a writer who gives so much pleasure should remain so essentially neglected: the unstopping, tissueless sentences travelling without delay of punctuation – those sentences which seem to drop a stitch and unravel just as you thought you were sewing up their meaning (“We lived here in the early years, in soft lands and climate influenced by the Severn, until my grandfather died and we moved to the big house a mile nearer the river where it went along below the garden”); the metaphors and similes, which float the strangest, rarest likenesses (a character’s eyes catching the light “like plums dipped in cold water”); the psychological subtlety, with its deep, delicate understanding of tragicomic fantasy; the authorial tact, content to let the reader move without explanatory signals, so that, as Coleridge said of Shakespeare, his characters “like people in real life, are to be inferred by the reader”; and above all the genius for speech, especially working-class, regional, and dialect speech, perhaps the greatest facility for the writing of dialogue in twentieth-century English fiction (less hammy than Kipling, more various than Lawrence, more inventive than Pritchett).

more from the TLS here.

Housekeeping

Frances Itani reviews in The Washington Post:Book_7

THE SPACE BETWEEN US by Thrity Umrigar

Sera Dubash, an upper-middle-class Parsi, lives a privileged, urban life, but her comforts largely depend upon her domestic servant, Bhima, who arrives every day to cook and clean for her. Bhima (based on a real-life Bombay housekeeper known to Umrigar when the latter was a child) lives in extreme poverty, under appalling circumstances in a city slum. She needs the job to survive. Although she lives in a crowded, stinking place where fresh water is scarce and there are abysmal, communal toilets and open drains, what Bhima allows herself to want is, on the surface, simple: a better life for her beloved granddaughter, Maya. But the opening pages tell us that this dream is already dashed. Maya, who has been attending college under Sera’s benefaction, is pregnant and is forced to abandon the education that offered hope of a better life. “Bhima wants to take the sobbing girl to her bosom, to hold and caress her the way she used to when Maya was a child, to forgive her and to ask for her forgiveness. But she can’t. If it were just anger that she was feeling, she could’ve scaled that wall and reached out to her grandchild. But the anger is only the beginning of it. Behind the anger is fear, fear as endless and vast and gray as the Arabian Sea, fear for this stupid, innocent, pregnant girl who stands sobbing before her, and for this unborn baby who will come into the world to a mother who is a child herself and to a grandmother who is old and tired to her very bones, a grandmother who is tired of loss, of loving and losing, who cannot bear the thought of one more loss and of one more person to love.”

Sera, a widow, and Bhima, abandoned by her husband, have a strong bond, but the differences are recognized by both. Every day, Bhima takes a break from the housework she does for Sera, and the two elderly women have tea and discuss their lives. Sera sits at the table, while Bhima squats on her haunches on the dining-room floor. There is always, as the title implies, a “space between.” But Bhima knows more about Sera than the educated Sera will ever know about her. Sera’s pregnant daughter and son-in-law live in her home, and her personal happiness now depends upon them.

More here.

The sins of the father

Rachel Cooke in The Guardian:

Milk_final Before I meet Edward St Aubyn, I swot up on him. Here are a few of the things that I read: that he wears too-tight tweed suits and green velvet smoking jackets; that he is facetious, arrogant and a terrible snob; that his manner is cold and his eyes like those of a ‘shark’; that his charm, wit and elegant sentences are reserved for close friends; that these friends include people with grand surnames of which I’m vaguely aware (Rothschilds, Guinnesses, Spencers) but am not smart enough to encounter at ‘weekend house parties’. And then, of course, there is the treacherous territory of the life from which he has, at Aubynbown64 least in part, hewn several novels. As a child, he was raped by his father. At 16, he was a spectacularly focused heroin addict. At 28, he decided that he would kill himself if he did not finish writing a novel. This is as forbidding a potted character analysis as any I have read.

Still, I was desperate to meet him. St Aubyn’s new novel, Mother’s Milk, is so good – so fantastically well-written, profound and humane – that all the other stuff, even the inhospitable biography, bleaches to grey beside it.

More here.

The caliphs’ tale

Reza Aslan enjoys Barnaby Rogerson’s history of the great Islamic schism, The Heirs of the Prophet Muhammad [And the Roots of the Sunni-Shia Schism].”

From The Guardian:

Prophet_finalOn the morning of his death, the Prophet Muhammad unexpectedly appeared before his followers in the city of Medina as they gathered for prayers in the makeshift mosque that also served as his home. No one had seen him for some time. Rumours were swirling around the city about his ill health. The Messenger of God was dying, people said, perhaps already dead. So when he suddenly turned up on that sunny morning in 632CE, looking stout and rosy if a bit greyer than anyone remembered, the anxiety about his health gave way to shouts of jubilation. A few hours later, when the prayers had ended and the congregation had dispersed, Muhammad slipped back to his room, closed his eyes and quietly breathed his last.

As news of Muhammad’s death spread through Medina, the elation that had accompanied his appearance at the mosque quickly transformed into raw panic. Muhammad had done nothing to prepare his followers for his demise. He had made no official statement about who should replace him, nor had he put into place the mechanism by which a leader could be chosen. It was as though the possibility of his death had not occurred to him.

More here.

Helium-3 and the future of energy

Anthony Young reviews Return to the Moon: Exploration, Enterprise, and Energy in the Human Settlement of Space by Harrison H. Schmitt, in The Space Review:

MoonLong awaited has been a book written by Dr. Harrison H. Schmitt, lunar module pilot on Apollo 17. Schmitt was the only trained geologist to fly on the lunar landing missions…

Schmitt graduated from Caltech and then went on to Harvard to receive his Ph.D in geology…

Schmitt does not see our return to the Moon as economically viable without private enterprise becoming integrally involved, and justified only if America and its partners return to the Moon to stay. That means a permanent base, and eventually several bases. Schmitt’s book acknowledges the need to exploit the Moon’s resources in situ. The chief motivation in returning to the Moon, writes Schmitt, is the potential for energy generation that is locked within the lunar soil. Helium-3, arriving at the Moon by the solar wind, is imbedded deep in the lunar soil as a trace, non-radioactive isotope. Schmitt says the energy in the raw lunar soil could be unleashed through the process of deuterium/helium-3 fusion. Small-scale fusion experiments have been taking place at the University of Wisconsin-Madison Fusion Technology Institute, where Schmitt is a professor. He discusses other means of fusion processes in context. What Schmitt envisions for the future are cargo ships returning significant quantities of lunar soil to Earth for processing by fusion for energy generation. He goes into considerable detail explaining the economics of making this viable.

More here.

He shoots! He scores!

David Runciman reviews Mourinho: Anatomy of a Winner by Patrick Barclay, in the London Review of Books:

In the United States, there has been a lot of serious academic research – and some not so serious – into the curious phenomenon of the Hot Hand. In all sports, there are moments when an individual player or whole team suddenly gets hot, and starts performing way beyond expectations. When this happens, the player or team seems to acquire an aura of self-assurance that transmits itself to supporters, fuelling a strong conviction that things are going to turn out for the best. This sense of conviction then reinforces the confidence of the players in their own abilities, appearing to create for a while a virtuous circle of infallibility in which nothing can, and therefore nothing does, go wrong. The quintessential instance of the Hot Hand (which gives the phenomenon its name) occurs in basketball, where certain players suddenly and inexplicably acquire the ability to nail three-point baskets one after another (in basketball you get three points for any basket scored from a distance of over 23’9’’, a formidably difficult feat which means even the best players miss more often than they score). When a player gets the Hot Hand, his or her team-mates know to give them the ball and let fate take its course. Anyone who has watched a game in which a player acquires this gift will recognise the feeling of predestination that descends on all concerned: players, spectators, commentators (above all, commentators) just know what is going to happen each time the Hot One lines up a basket from some improbable position on the court. He shoots! He scores!

What the research shows is that all this – the sense of destiny, the effect it has on a player’s confidence, the virtuous circle – is an illusion.

More here.

Tart imitating life

Christopher Buckley reviews Dog Days by Ann Marie Cox (of Wonkette fame), in the New York Times:

Cox184Ana Marie Cox burst onto the scene in 2004 when her political blog, Wonkette (“Politics for People With Dirty Minds”), identified Jessica Cutler as the Capitol Hill staffer who was detailing her lurid sexual escapades on a blog called Washingtonienne. Cutler herself has now written a novel about her affairs with various D.C. Mr. Bigs. It goes without saying that a TV series is said to be in the works. What hath Candace Bushnell wrought?

In “Dog Days,” Cox’s brisk, smart, smutty, knowing and very well-written first novel, the 28-year-old protagonist Melanie Thorton, a Democratic presidential campaign staffer, diverts media attention from her candidate’s political troubles – and her own romantic ones – by creating a fictitious blog supposedly written by a local libertine calling herself Capitolette. (Yes, rhymes with toilette.)

Thus we have a case of tart imitating life.

More here.

Saturday, January 7, 2006

How to stop Venice from being swallowed by the sea

Ted O’Callahan in Seed Magazine:

VeniceVenice is sinking beneath the sea. But a group of engineers believe that sea water, itself, may be the best way to save the city.

Giuseppe Gambolati heads a team of researchers who, last month, presented city leaders with a proposal to inject sea water into an aquifer deep below the city. He predicts this will raise the ground level as much as 30 cm over the course of 10 years.

Gambolati has worked on land subsidence issues for 30 years and he says that the technique has been used effectively in other places where the ground has begun to sink. He cites Long Beach, California, where subsidence (sometimes 9 m deep) resulted from oil production; they’ve been using water injection successfully since the 1950s.

More here.

Cantonese Is Losing Its Voice

David Pierson in the Los Angeles Times:

21246325Carson Hom’s family has run a thriving fortune cookie and almond cookie company in Los Angeles County for 35 years.

And for much of that time, it was a business that required two languages: Cantonese, to communicate with employees and the Chinese restaurants that bought the cookies, and English, to deal with health inspectors, suppliers and accountants.

But when Hom, 30, decided to start his own food import company, he learned that this bilingualism wasn’t enough anymore.

He checked out the competition at a recent Chinese products fair in the San Gabriel Valley and found that he couldn’t get much further than “hello” in conversing with vendors.

“I can’t communicate,” said Hom, whose parents are from Hong Kong. “Everyone around used to speak Cantonese. Now everyone is speaking Mandarin.”

Cantonese, a sharp, cackling dialect full of slang and exaggerated expressions, was never the dominant language of China. But it came to dominate the Chinatowns of North America because the first immigrants came from the Cantonese-speaking southern province of Guangdong, where China first opened its ports to foreigners centuries ago.

More here.

An Interview with Robert Jervis

The transcript of Harry Kriesler’s interview with International Relations theorist Robert Jervis is up at Conversations with History.

Let’s talk a little about international relations theory and doing it. What does it take to do that work well, in terms of skills, in terms of temperament?

That’s interesting. Of course, now skills is one of the right words. A tremendous amount of [work] was either formal, using game theory (and I use informal game theory, but a lot of people do it formally), and a lot large statistical analyses. So, any young person has to learn that. I read the stuff. I’m — you can tell from my expression — I’m ambivalent. It has produced some real value. There are a lot of different ways to study, there’s no one method, no one approach, but it takes a fascination with international politics. Every day I either pick up the newspaper or a history book and say, “I can’t explain that. Why did that happen?” You know: “What rules does that violate?”

It takes a combination of thinking about particulars and trying to think about the generalizations it fits with, or can lead to, or can contradict. That playing back and forth between the particular and the general is what is certainly most productive for me. It’s a constant grounding in saying, “Well, wait a minute,” keeping your theory anchored in something.

I’m familiar with your work, and we’ll talk about some of it in a minute, but I’m curious, given this background that you’ve just described, there must be a fascinating interplay between the theorizing you do and what’s happening in the world or what has just happened. Talk a little about that, and maybe give us an example of that, because I know, for example, you’ve done a lot on nuclear weapons.

Let me give you two of my favorites. One is what I’ve written about in the misperception book and in other articles about the security dilemma on the extent to which a conflict can be seen as irreconcilable conflict of interest in which a defender of the status quo, to be crude about it, has to use threats and enforced deterrence, it’s called, versus what I call — they’re drawing on others, I am not original in this — in the spiral models.

But basically this is what I grew up with. When I asked my parents in 1947 — the Russians have shot down this plane over the Baltic, claiming it was a spy plane. How ridiculous that we would spy, of course not. But leave that aside. What I was asking then was the same question, so that I’m still driven by those questions.

Naipaul’s Magic Seeds

Lester Pimentel reviews V.S. Naipaul’s Magic Seeds, in PopMatters.

“It is wrong to have an ideal view of the world. That’s where the mischief starts. That’s where everything starts unraveling.” The apercu belongs to Willie Chandran, the peripatetic protagonist of V.S. Naipaul’s latest novel Magic Seeds. More than his other works, this didactic cautionary tale about the perils of utopianism crystallizes Naipaul’s essentially conservative worldview.

Naipaul’s transformation — from avatar of post-colonial angst to Thatcherite apostle — mirrors Willie’s own ideological peregrination. The political has always been personal in Willie’s life. He is, after all, the child of a politically inspired union, as we learned in Half a Life (2001). Moved by Gandhi’s calls for a life of sacrifice and the rejection of old values, Willie’s Brahmin father marries a lower-caste woman for whom he feels nothing but repulsion. The father’s obvious regret and disdain, combined with the mother’s upper-class pretensions and ambition, make for a miserable marriage. Willie, desperate to get away from such a toxic household, jumps at the opportunity to attend university in England. After fully immersing himself in the hipster culture of 1950s London, Willie meets Ana, a Portuguese-African estate heir whom he weds and follows to a decrepit East African colony (Mozambique). For 18 years, Willie inhabits the “half-and-half world” of “second-rank Portuguese” — the mixed-race ruling class to which his wife belongs. With tribal conflict looming in the wake of a guerilla war that expels the Portuguese colonial regime, Willie, tired of “living my wife’s life,” abruptly breaks off his marriage to Ana.

close reading, bad

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A specter is haunting the academy—the specter of close reading. But don’t worry: as the New York Public Library had the Ghostbusters, the academy has Franco Moretti.

Of course, Moretti is not the first or the only critic to object to close reading. For a good fifteen years, close reading has had a place in the ever-expanding group of things that might be bad for you; experts have shown that close reading will cause you to ignore history, reinforce cultural hegemonies, and “avoid commitment.”

But Moretti’s objections are different. Moretti is a man of the world, and men of the world do not reproach you for trying to avoid commitment. Instead, he finds close reading to be close-minded, superstitious, a fundamentally “theological exercise—very solemn treatment of very few texts taken very seriously.” The problem with the canon, by extension, is not that it is sexist, racist, or classist, but that it is so—provincial.

more from n+1 here.

Explaining variation in Darwinian evolution

American Scientist Online interviews Marc W. Kirschner and John C. Gerhart, authors of The Plausibility of Life: Resolving Darwin’s Dilemma.

Can you describe the new theory [of “facilitated variation”] briefly?

Our theory addresses the most mysterious part of Darwin’s theory of evolution, namely “variation.” As you may recall, he postulated that small differences of form and function inexorably arise among individuals in any group of animals. One individual, bearing its variation, may be more fit than others of the group to survive and reproduce in the environment at hand. In time, its descendants out-reproduce the others and come to replace them.

About half a century ago, we learned that heritable variation does not occur without mutation. Any place in the genome can suffer mutation, which is a change of the local DNA sequence. It appears to strike at random, and rarely. Our theory of “facilitated variation” is meant to explain how rare and random mutation can lead to exquisite changes of form and function.

We give center place to the fundamental processes by which animals develop from the egg to the adult and by which they function as adults. These are the “conserved core processes.” They make and operate the animal, and surprisingly they are pretty much the same whether we scrutinize a jellyfish or a human. There are a few hundred kinds of processes, each involving tens of active components. Each component is encoded by a gene of the animal’s genome, thus using up the majority of the 20,000 genes possessed by complex animals such as frogs, mice and humans.

agee revival

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There’s seems to be something of a James Agee renaissance going on these days. This is a damn good thing. James Agee was one of the best things in American criticism and literature. Here’s a piece from David Denby at The New Yorker:

The mixture of piety and blasphemy is what makes Agee’s fiction so moving, for here is a Christian author of self-punishing temperament who, at the same time, was awed by creation and could not allow a single aspect of sensuous experience to go unadmired—which meant, necessarily, loving what was raw and degraded as much as what was seemly and fine. In “The Morning Watch,” an autobiographical novella of 1951, a twelve-year-old boarding-school boy, asleep in the early morning of Good Friday, dreams that he is Jesus about to be betrayed by his disciples. He awakes, and hears not Peter and Judas but sleepy boys cursing all around him. He goes to chapel and there, on his knees, relives the previous months of religious crisis, during which he tormented himself over masturbation, only to realize that, at that moment, his back and thighs hurting as he kneels, he is committing the sin of imitating Jesus’ suffering. He leaves chapel with his friends and, as they go skinny-dipping at dawn, steals a look at their genitals; then, at the side of the pond, he kills a snake that may be poisonous and feeds it to the school’s hogs. The mood swings back and forth between guilty devotion to Jesus and excited apprehension of the physical world. As the school enters Easter weekend, and Christ’s resurrection approaches, the boy eases into his sexual future.

The Supreme Court and liberal drift

In the Boston Review, Jon D. Hanson and Adam Benforado on how the Supreme Court makes justices more liberal.

While there have been a number of relatively reliable conservative justices over the years—Antonin Scalia, Clarence Thomas, and Rehnquist being prime examples—and some important right-shifting exceptions—notably Felix Frankfurter, appointed by Franklin D. Roosevelt, and Byron White, appointed by John F. Kennedy—the tendency in recent decades to drift leftward has been strong enough to gain both popular and scholarly attention. Indeed, Larry J. Sabato, the director of the University of Virginia Center for Politics, has suggested that about one quarter of confirmed nominees over the last half century have wound up “evolving from conservative to moderate or liberal.” . . .

So what actually accounts for this juridical drift? The short answer is that we are not who we think we are. Our inability to predict jurisprudential shifts of Supreme Court justices reflects a much broader phenomenon known to social psychologists as the “fundamental attribution error.” As countless experiments have shown, we generally assume that behavior is controlled by personality, attitudes, choice, character, and will. But these “dispositional” factors are often far less significant than “situational” factors such as unseen features of our environments and subconscious processes within us. By allowing disposition to eclipse situation, we often misunderstand why people behave as they do—and thus are surprised when our predictions fail. . .

At least three types of situational influences can have a large effect on a judge’s behavior and, hence, the extent of their juridical drift: the first is the unusual array of forces that sets judging apart from other lawyerly occupations such as legislating or advocacy; the second is the particular background and experiences of individual judges; the third is all the forces external to the court—including think tanks, the media, the academy, and public attitudes—that appear to strongly influence the judicial decision-making process.