Pharmacogenetics

Nothing titillating for this post. Just a new PNAS paper that provides a nice example of pharmacogenetics: Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin.

David Goldstein’s group at University College London have identified genetic variations associated with dose response to two anti-epileptic drugs (AEDs): phenytoin and carbamazepine. A broad range of doses are used with these drugs, and the final “maintenance” dose for each patient is normally determined by trial and error.

In this paper, they report that a known functional polymorphism in the CYP2C9 gene is highly associated with the maximum dose of phenytoin (P = 0.0066). They also show that an intronic polymorphism in the SCN1A gene shows significant association with maximum doses in regular usage of both carbamazepine and phenytoin (P = 0.0051 and P = 0.014, respectively).

How does a polymorphism in an intron affect drug metabolism?

This polymorphism disrupts the consensus sequence of the 5′ splice donor site of a highly conserved alternative exon (5N), and it significantly affects the proportions of the alternative transcripts in individuals with a history of epilepsy.

If their findings are corroborated, genotyping could be used by doctors to more quickly determine the proper maintenance dose for these drugs.

Here are some fun parts from their discussion:

We have associated functional polymorphisms with the dose used in regular clinical practice for two leading AEDs, phenytoin and carbamazepine. For phenytoin, a well known low-activity variant in the CYP2C9 gene associates with dose, as does a functional variant in the SCN1A gene, encoding the target of phenytoin. The SCN1A variant is also highly associated with dosing of carbamazepine, thus providing functional replication of the effect of this variant. This functional replication, together with the apparent function of this polymorphism, makes a strong case that the association reported here is real. However, although the case made here is compelling, as is usual with association genetics, our results cannot be considered definitive or ready for clinical application until they are confirmed by independent replication. To our knowledge, this SCN1A variant is the first polymorphism in a drug target associated with the use of an AED and one of only a handful of target polymorphisms for which there is strong evidence of an effect on clinical drug use (22). Furthermore, our study demonstrates the pharmacologic significance of alternative splicing in a human sodium channel. Although there are other examples of alternative splicing in other human sodium channel genes, none has been associated with functional effects (23).

This polymorphism is potentially of more general importance because of the prominence of sodium channel blockade in the treatment of epilepsy (and other neurological conditions). For example, more than half of epilepsy patients treated pharmacologically in the United Kingdom receive a drug that principally targets the sodium channel (24).

Concluding:

Our results support the view that the major target, transporter, and drug metabolizing enzyme are good starting points to study drug response and that pharmacogenetic traits, therefore, are more tractable for genetic analyses than are those for common disease predisposition (22). We also emphasize that a haplotypetagging strategy (14) identified a previously unknown functional variant in the SCN1A gene. This functional variant was found 91 bp away from the nearest exon known at the time of the study, illustrating the need for exhaustive tagging.

Overall, our findings suggest that using genotype data may make it possible to safely reduce the time required to reach an effective dose. Therefore, it is also a priority to assess the utility of dose adjustment on the basis of genotype for these medicines in a prospective clinical study. Prospective studies of carbamazepine and phenytoin, informed by a detailed retrospective study, would also serve as a useful model for future pharmacogenetic studies (25).

Posted by rikurzhen at 12:06 AM

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Evidence for natural selection between populations

In February we discussed a new Science paper, Whole-Genome Patterns of Common DNA Variation in Three Human Populations.

They genotyped 1.6 million SNPs in 71 unrelated individuals from three populations: 24 European Americans, 23 African Americans, and 24 Han Chinese from the Los Angeles area. While this was a tool building exercise, they did perform a number of interesting analyses on the data they collected. One that caught my eye was an analysis that looked for evidence of selection between populations. Their analysis made use of Fst calculations (a measure of how much genetic variation is between rather than within populations) for each SNP. In summary, they found that Fst was higher for SNPs in gene-containing (genic) regions than gene-poor (nongenic) regions and that Fst was higher in coding than non-coding regions. Put another way, there is greater genetic variation between the populations in the regions of the genome that are most likely to be functional. These differences were small but significant. They interpret these findings as evidence for local selection. However, when they asked the question of whether the SNPs that provided evidence for natural selection were private to a single population, they did not find this to be true. From this they conclude that most functional genetic variation is not population specific.

Any one interested in looking at this closer can find the data online here. It might be interesting to ask which genes are associated with SNPs that show high Fst.

Here is the associated text from the paper:

Evidence for natural selection between populations. It has been suggested that natural selection distorts the observed distribution of FST across the human genome and that large FST values can be used to identify candidate loci likely to have undergone local selection (13, 19). If this is true, then larger FST values should be found near functional genetic elements. We looked at the distribution of FST for SNPs that were genic or nongenic, coding or noncoding, and synonymous or nonsynonymous. We performed the analysis within subsets of SNPs grouped by MAF, so that effectively, we looked at the fraction of between-population variance for SNPs with the same total genetic variance (fig. S3). Common SNPs in genic regions do have slightly but significantly higher FST values than nongenic SNPs with the same MAF [analysis of variance (ANOVA), P = 1.8 x 10–46], and common coding SNPs have slightly higher FST values than noncoding SNPs in genic regions (ANOVA, P = 1.1 x 10–4). We did not see a significant difference in FST between synonymous and nonsynonymous coding SNPs, but our sensitivity is limited by the small sample sizes and expected correlations among SNPs within the same transcript. These results are consistent with local selection changing the distribution of FST near functional sequences. However, because the distributions of FST among genic and nongenic SNPs are very similar, large FST values by themselves appear to be very weak evidence of selection.

We performed a similar analysis to see if there is also an association between private SNPs and functional genetic elements. When conditioned on MAF, we saw no difference in frequency of private SNPs among genic and nongenic SNPs or among coding and noncoding SNPs (fig. S4). This indicates that the SNPs responsible for evidence of local selection in the FST analysis tend not to be private and instead are segregating in multiple populations. Although there are known examples linking population-specific SNP alleles to phenotypic differences (20–22), our results are more consistent with the conclusion that most functional human genetic variation is not population-specific.

Posted by rikurzhen at 12:43 AM

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"How many did you have?" "Four!"

Saturday’s New York Times“We are using too many raw materials to sustain this growth,” said Pan Yue, China’s environment minister, in a recent interview with the German magazine Der Spiegel. “To produce goods worth $10,000, for example, we need seven times more resources than Japan, nearly six times more than the United States and, perhaps most embarrassing, nearly three times more than India.Are you telling me there’s room for the price of Chinese manufactures to go even lower?

Don’t tell Wal-Mart.

Posted by jeet at 11:15 AM

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Spencer Wells' Next Project

Spencer Wells, working with The National Geographic Society, has bold ambitions to resurrect the ill-fated Human Genome Diversity Project with plans to sample 100,000 blood samples from indigenous populations from around the world. Nicholas Wade reports in the New York Times:

The program is an effort to accomplish the goals of the Human Genome Diversity Project, an initiative that was proposed by population geneticists in 1991.

That project ran into a political furor that prevented it from receiving substantial government support. It was denounced by some cultural anthropologists, who said that looking for genetic differences among populations was tantamount to racism. And advocates for indigenous peoples portrayed it as a “vampire project” for extracting valuable medical information from the blood of endangered tribes while giving nothing in return.

The proponents viewed their plan as complementing the Human Genome Project, then getting under way, because it would show how the sequence of DNA units in the human genome varied from one population to another. The project did proceed on a more modest basis, eventually collecting blood samples from 52 populations that were converted into 1,000 cell lines. The first major analysis, published in 2002, showed that the subjects’ genomes fell into five major clusters corresponding to their continent of origin and, in effect, to their race.

Of course, the critics are already staking their ground.

But Dr. Kenneth Kidd, a population geneticist at Yale University, expressed reservations about the plan to preserve the blood samples as raw DNA. Because the DNA is finite, it cannot be shared with every scientist who may ask for some. In the Human Genome Diversity Project, by contrast, white blood cells from a sample were made essentially immortal before storage. Though it would cost an additional $200 to $300 to immortalize each sample, the cells last forever and the supply is inexhaustible.

Dr. Kidd you may recall co-authored a paper with Dr. Robert Sternberg in the American Psychological Association’s last attempt at obscurantism on the question of whether race is more than a folk taxonomy.

My personal hope is that the power of the cultural anthropologists has waned from their heydey a decade ago, especially in light of the remarkable advances in genetic sciences, and that the same forces that killed the Human Genome Diversity Project a decade ago can’t today marshall the forces to take on the celebrity of Dr. Spencer Wells, the intense public fascination with this type of research and the reach and respected brand of the National Geographic Society.

Addendum from Razib: Check out The Genographic Project over at National Geographic. Spencer Wells is a maverick scientist without an academic affiliation, and The National Geographic Society is not a traditional “Ivory Tower.” The results aren’t always pretty, but as Craig Venter showed, those who work outsides the “establishment” channels can shake things up and affect more change on the dynamics of The System from the outside than from within. Spencer Wells might very well be the monster that Richard Lewontin birthed….

Update from Razib: Radio interview with the lead researcher on the project (not Spencer Wells, some British dude).

Posted by TangoMan at 09:09 PM

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Heretical reflections and projections

As all of you know John Paul II has passed. Unlike many I have few strong opinions about the last Pope. My interests tend to skew toward the past rather than the present, as the latter is often a deceptive slice of the canal that the world uses to glide through time. After all, old Jules Verne can tell you all about the steam driven paradise of 2000!

Nevertheless, the Church as an institution is of great interest. A plain assertion should suffice. Qualitative references would also convince most. But to get a true handle on its significance, consider the numbers. Over 1,000,000,000 followers. 2,000 years, 100 generations, of uninterrupted history. The dominant religion in Latin America, the most numerous confession in Europe, North America and Australasia, and possibly Africa. In Asia, the only Christian majority nation is Roman Catholic, while in South Korea the past two presidents have been Roman Catholic. To understand the world you need to brush against the reality of the Church. Its hand extends through both time and space, and no doubt it will continue to reach out into the future.

The title, “Heretical reflections and projects,” is grounded in the reality that I am an unbeliever, and strictly speaking I am a “heathen” rather than a “heretic,” I make no pretense toward True Belief and never have. My own personal background colors my perceptions of the concrete manifestations of the Church, the people who profess loyalty to the Bishop of Rome as the heir to the rock of Christ’s original Church and the “smells and bells” which mediate the Roman Catholic religious experience in the physical realm. As a child my peers were overwhelmingly Roman Catholic. This I know because every Tuesday the Roman Catholic children at my elementary school left class one hour early and engaged in some Church related activities. Those who were left behind were a pathetic remnant. My classmates were mostly of Irish or Italian extraction, culturally as well as religiously embedded in the Church. When I reached adolescence my experience of Roman Catholicism shifted greatly as I moved to a locale where Mormonism and evangelical Protestant Christianity were the dominant faiths. My classmates who were evangelical Christians peculiarly distinguished between “Christians” and “Catholics,” as if the latter were not simply a subset of the former, while my Mormons friends tended to exhibit more hostility toward the Roman Church than other traditions because of their perception that it was in Rome that the purity of the original Christian doctrine was fully debased with philosophy.1

From a purely personal perspective my own religious influences buffetted me in anti-Catholic directions implicitly. Though never a “believer” in a deep sense, and in fact an explicit and conscious atheist by my 8th year, I was soaked in the cognitive inputs of a conventional Islamic faith. This shaped my mental “templates” or schema toward specific responses to a given range of inputs. Much of life is not conscious, reflexive rather than reflective. As a child I learned little of Christianity, rather, my parents were shaped by a South Asian milieu where Hinduism was the great “rival.” In their social interactions Hindus still loomed large in the small circle of South Asians who began to form networks in the early 1980s. And so my mother told me of the Hindus, their love of dance, music and idolatry. Their fixation on bright colors and bestial gods. She made it clear that I must be wary of their temptations, their faith was the anti-thesis of the One True God who we worshipped. On a conscious level I disregarded much of what I was taught, and yet in hindsight it is quite clear that my Islamic “indoctrination” shaped particular cognitive reflexes which were to color my experience with the world around me for years.

My parents occassionally went to social events that were fixed at a local Presbyterian church. It was a rather plain and spare creature of an older austere Protestant tradition. And yet there was a room that elicited in me a profound unease: the worship hall (?). Though now I realize that the depiction of Christ with his disciples was a rather low key affair as far as such representations went, I was still disturbed that there could be so much color, such an explicit depiction of the human form, in a place of worship! At the time I had a hard time elucidating to myself why I was so disturbed, but now I suspect that background schemas were being triggered, my mental reflexes cued toward “Hinduism” were being tripped and automatic responses were washing over me. Keep in mind that I was already an unbeliever in gods at this point, nevertheless, the past of religious inculcation leaves a deeper footprint that many of us heathens are willing to admit. One can imagine my response to a Roman Catholic Church, with all its pageantry and lush color. While a person of Catholic origin, whether they believe or not, might experience through the visual depiction of their central religious motifs a connection with an ancient Church and a deep and rich faith, essentially opposite schemas of revulsion at “idolatry” seem to well up from my self-consciously iconoclastic being.

But the past is past, and we are more than creatures of schema, we can reflect and transcend our instincts if we so choose. My perception of the Roman Catholic church on a more cerebral level became mixed as I matured as a human being. On the one level in the contemporaneous context I saw in Roman Catholics “reasonable” religious people who had made their peace with modernity, as opposed to evangelical Christians who revolted against the consensus of modern science (especially evolutionary biology) or Mormons who set themselves apart as a “special” people. And yet intellectually I was also discovering the rich past of the Western tradition, of Greece and Rome, and I began to empathize with the last of the pagans, with the pagan Prefect of Rome, Symmachus, who pleaded for religious tolerance to that most orthodox of Emperors, Theodosius, or Damascius, the last head of the Platonic Academy, heir to an admittedly debased pagan philosophical tradition that stretched back 1,000 years to Thales and Heraclitus,2 who fled with his followers the religiously sanctioned closure of his school under the Emperor Justinian.3

The Church which I found to be a reasonable, intelligible, institution of the modern world I found to be the hand which suffocated the classical world. History is more complicated than a few spare generalizations or naked assertions. But, I will state now that I do not necessarily think that the incipient Church killed the classical world, nor do I think it was a necessary condition of the transmission of that world’s intellectual traditions into the future. The past is the past, and I have made clear in the past that words have great power, but can also deceive. The Church of John Paul II was never the Church of Gregory the Great. Thomas Hobbes said that “The Papacy is nothing other than the ghost of the deceased Roman Empire, sitting crowned upon the grave thereof.” But even ghosts change, their essence shifted by the sands of time so that they become wholly different spirits altogether. How many Roman Catholics know that the term “diocese” is derived from the name of the last and greatest persecutor of Christians, Diocletian? (please see the erratum below!)

The Roman Catholic Church was gestated by the West’s first universal Empire. It still bears the hallmarks of that infancy and childhood, but adulthood has transmuted its character so that there is no central essence, rather the Church is
an enormous empire of mental predispositions and physical institutions, woven together by the glue of common credos and verbal affirmations, affixed into one whole by a shared historical experience. Where I live, breathe and exist, the Church is generally no friend of “theocracy,” for though it is the largest of religious bodies it is not a dominant one. Additionally, the intellectual elite of the Church has long made its piece with the practice of science and even ingeniously coopted the more provocative findings of the profane as simply manifestations of the sacral.4 On the other hand over one century in the past the Roman Catholic Church was an enemy of liberal nationalism, hostile to such an extreme that the Pope refused to leave the Vatican grounds and venture on to the soil of the newly constituted Italian republic. In places like Ireland or Chile the Roman Catholic Church remains a powerful institution that informally constitutes an “estate” or “pillar” which must be consulted publically on the issues of the day. In South Korea the Roman Catholic Church was identified with dissent from the dictatorial regimes of the past, and now is the faith of choice for an avante guarde affluent bourgeois which is the most advanced in the long march to post-Confucian liberalism. In much of Latin America the Roman Catholic Church became identified with elites and authoritarian regimes, to the extent that the underclass in Chile has been effectively ceded to the Pentecostal movements. In contrast, in other Latin American nations the Roman Catholic Church is strongly infused with Leftist libertarian theology. In 18th century France the Roman Catholic Church was identified with the peasantry who dwelt far from Paris, and they were the bedrock which served as the springboard for several savage revolts agains the tyrannies of the Republic and the Cult of the Goddess Reason. In the 4th century the pagani were the rustics who worshipped the old gods, and the Christian Church was an institution of the cities and the market towns. Christian intellectuals even mooted the possibility that the semi-humans of the country even need not be introduced to the One True Faith, and in fact deep into the medieval period, that symbolic apogee of unified Christendom, many of the country folk were operationally pagan in personal piety if not outward genuflection. With the breaking of Christendom into factions in the 16th century there was a renewed emphasis on inner belief and proper outward orthodoxy among both Catholics and the newly arisen Protestant movements. The collapse of de facto Roman Catholic universalism in the West gave rise to a need to enforce “orthodoxy” across the width and breadth of society, proper Christian behavior was no longer the reserve of monastic communities who lived the sacred life on behalf of profane society.

My point in tediously restating facts, some well known, and some not known, is to suggest that the One True Church is a cognitive illusion, bound together by shibboleths of verbal fealty which trigger wide-ranging allegiances built upon the gossamer threads of the reflective rational mind. This does not negate the importance, the salience, the predictive power in sociological models of the “Catholic mind,” but the reflective mind is only a small portion of who we are, and a far less significant fraction of our decisions and behaviors are controlled by its precepts and preconceptions than we might think. This is perhaps illustrated in the fact that the greatest mother of doctrinal heresy in Christendom has been the Church itself. Arius was a presbyter and Luther was a monk. Even today the Church is affiliated with intellectuals who run the full spectrum of opinion and assertion, all tenuously unified by affinity to a common verbal creed, a doctrinal unity affirmed at rare intervals. Until the raw schismatic energy of the Radical Reformation5 was unleashed heresy was the province of the clerical caste itself, after all, the Hussites followed a priest. Additionally, Catholic ritual and practice as it is lived varies a great deal, from the cool discipline of the Germanic confessions to the old indigenized traditions of Latin America or the new African congregations which draw upon models of the primitive Church to justify their dabbling in old magics. All shed tears over the death of the Polish Pope, and yet all live their faith in radically different ways. This is nothing new. The tale of the decline, absorption and assimilation of the “Celtic Church” toward the Roman fold is well known, beginning during the age of Gregory the Great, maturing during the reign of Brian Boru, finally culminating in the identity of Celtic Irish identity with Roman Catholic faith during the Cromwellian period. But who tells the tale of the Visigothic liturgy which disappeared after 1000 as the kingdoms of northern Spain once more became part of the Christian world as Al-Andalus retreated? What of the Anglo-Saxon translations of portions of the Gospel by the Venerable Bede? What of the living alternative traditions of the Eastern Rite or the Syrian Christians of Kerala?

Over one billion individuals on six continents are “unified by diversity,” but that diversity is not new, it has been part and parcel of the Church since its beginning. Today many secular intellectuals think of the Church as a conservative institution, but this was once the institution which rose to rival the Roman Empire itself, dissenting from its claims to authority and giving birth to radical and sometimes violent movements like the Montanists. And yet in the 4th century it went from being the counter-Rome to fusing with the institutions of the Roman state itself, so like the minerals that suffuse and replace the original substance of bone but retain the general structural condition, the Roman Catholic Church is the one last uninterrupted remnant of the first universal Empire, an age when the power of European potentates stretched from the Scottish moors to the banks of the Euphrates, from the deserts of Libya to the mists of the North Sea. The Roman Catholic Church is like an ancient cloak, stretched out over nations, even continents, retaining crucial elements of its original fabric as those who don the raiment pass through the revolving door of history.

Which brings me to what I believe is one of the threads which binds the Church of the past with the Church of the present, the Church of the second century with that of the third millennium. And that is internationalism, universalism, transnationalism. Some nationalistic thinkers who are nonetheless faithful Roman Catholics attempt to argue that their faith supports their particularistic political beliefs. Certainly Franco used the Church to buttress the Spanish state (though he won the Civil War with many North African troops!). Charlamagne used the Roman Catholic faith to unify his many subordinates, and waged wars of religious conversion against the pagan Saxons on account of his God. We can weave from the axiomatic creeds whatever patterns we wish to see in them if we wish to pay the price of intellectual contortion. And yet at the most basic level I think one thing that must be remembered is that the ancient is often preferred to the more recent in the religious pantheon of ideas. Though the medieval period was characterized by fragmented states, some Catholic authors argue that the Church was a cosmopolitan glue (there were Syrian popes even after the rise of Islam!). And projecting back into time, the chrysalis of the Church was the universal Roman Empire, a political entity where citizenship spanned oceans and languages. As the chrysalis of the Empire was shed the Church took upon itself a new role that transcended the bounds of the barbaric realms which
arose in Western Europe. The man who brought Christianity in its official form to the English was an Italian by birth, while the early missionaries who founded monastaries in the heights of the Alps during the Merovingian period in the 6th and 7th centuries were of Irish origin.

How much do models, historical precedants, truly matter? The common binding of Catholic faith did little to prevent the Bavarians from slaughtering fellow believers in the 19th century under Prussian Protestant officers. The Catholic French intervened on behalf of Protestant German princes against the Holy Roman Emperor, on account of the commands issued by a Cardinal of the Church no least! The power of the reflective mind to shape history must be tempered by the reality that this mind can reshape the past in its own image. The Normans of Sicily were defenders of the faith, nevermind their Muslim bodyguard! Nevermind the brutal harm that they did to the Byzantines by periodically assaulting them from the West. Nevertheless, the officers of the Church are educated men, and I suspect that on the whole the commanding heights are dominated by men who live through their reflective mind. Unlike all of us moderns they know Latin and can read the classics in the originals, and not just the pagan authors, but their own clerical ancestors. And they perhaps recall that St. Augustine taught that the pagans of Rome who declared that the Visigothic sack was punishment from Rome’s old gods were denying the primacy of the City of God, that no matter the material descent of the world it was spiritual salvation that mattered. Augustine and other Church Fathers declared that the universal Empire was simply the predecessor of the universal Church, that its existence was simply a precondition, a tool, for the Gospel to spread through the known world, that brotherhood before God transcended kin and kith in the final calculus.

Such extravagent idealisms are not necessarily the norm, especially in an institution headed by the Prince as well as the Pope. But, in our world the Prince is long dead, and the power of the Roman Catholic Church is more spiritual than temporal, as it was during the times of Rome. And as in the Roman days it is simply another institution among others, and in many nations it is one confession among many.

So…to projections. Those who wish for the ressurection of a muscular, medieval, nationalistically friendly Church, will I think be disappointed. If you read later pagan intellectuals like Zosimos you see that it was the Church which was the noveau force in society, which pushed radical changes and departed from the traditions of the ancients. The pagan rearguard action to cherish the old ways often dissipated in the face of Christian triumphalism. In his debate with the aforementioned Symmachus St. Ambrose declared “There is no shame in passing to better things.” Out with the old, in with the new and true. We live in the afterglow of an age when secular intellectuals declared that a post-Christian era was one of those “better things.” Despite the protestations of those who show that the populace in most nations are still believers, we must look beyond the platitudes and into the hearts, and I suspect that in our everyday life we are extremely de-sacralized. I will avoid explaining this process, whether it be the atomizing influence of Protestantism and a Catholic Reformation, or the acidic power of “modernity.” I simply state that operationally in many ways Christians do navigate a pagan world, where Caesar mouths the words that give dominion to Christ, but retain the powers of this world for their own ends. Some conservatives applaud the possibility of a Third World Pope, while others fear such a transition of power away from the continent which incubated Christianity for 2,000 years. I suspect that the change is inevitable, just as the original Jewish Church became a Greek Church, and a Greek Church became a Roman Church, and the Roman Church became a European Church. Today it is truly rather close to a Universal Church, and the new believers, the new officers of the faith, arise from soil untouched by 2,000 years of European history. They will look to the 4th century, not the 14th. Their rejection of female priests and homosexuality is not drawn from a European traditionalism, but a human traditionalism, a traditionalism which was often (contrary to Christian stereotype) shared by pagan intellectuals of old.6 African priests today argue that magical exorcisms and other rather antiquated practices draw upon the same tradition as the ancient Church. The new officers will not look to the examples of the Popes of the “Age of Discovery” who partitioned the pagan world between European superpowers, rather, they will look to more ancient and authoritative models of righteous and radical piety in the face of Caesar, awash in a cosmopolitan world and perhaps unrepentant of the decay of the pagan cities in which their faith flowers.

Many Western liberals, secular, often from non-Roman Catholic post-Protestant and post-Jewish backgrounds, depicated the last Pope as a “conservative.” Such words are loaded with all sorts of peculiar and contextually framed inferences. I do not believe that the last Pope was “conservative” in the context of the Princes who ruled the Church for a thousand years after their grant of land from Charlamagne. The last Pope was not a “conservative” like Pius IX, I believe he had made his peace with the liberal democratic nation-state. The “conservatism” of the last Pope was in many ways the conventional conservatism of the human race, patriarchy, sexual separation of roles and a bias toward procreative relationships. Such things many who are not Catholic, but non-Western, or pre-modern, could have seen as “normal” or “conventional.” Why such biases are conventional I will forgo for another day, but nevertheless I do not see in the Church a radical reactionary spirit, rather, it is a reflection of norms which dominate the non-Western world but have become out of place in the post-Christian West. And the ancien regime is gone, rather, the days of Rome are at hand, a cosmopolitan gaggle of transnational corporations and a post-ethnic corporate elite travel the world as if the Pax Romana had stretched its hand over the world. So, I predict a return to the form and mode of the ancient Church, oppositional, radical and profoundly other-worldy in the eyes of the powers that be. There will be no ressurection of the old Western order which coalesced out of the machinations of Gregory the Great and the compromises made with barbarian warlords after the fall of the Western Roman Empire. We live an age cognate with that of the era after The Edict of Milan, but before the Council of Nicea, the Church ascendent is no more, but neither has another Diocletian arisen….

Take home: The Church may be an organically developed creature, but its raison d’être was always to be a proposition propogation machine.

Erratum: Dienekes pointed out to me that diocese is a Greek term, and not derived from the name Diocletian. My confusion was caused by the fact that Diocletian’s administrative reforms resulted in the diocese attaining some level of atomic importance during his reign, along with the decline of the provincial unit (which was too large). In any case, my error does not undermine my general point, that with the establishment of the Church as the official religion of the Empire it coopted imperial forms and institutions to the point where it was the standard bearer for romanitas once the civil and military edifice fell by the wayside. And to some extent it remains the voice of romanitas in the modern world.

1 – Of course, it was in the Greek Church that the greatest philosophers of the early Ch
urch made their contributions. Men like St. Augustine were in many ways clarifiers of truths originally exposited by thinkers like Origen.

2 – The Neoplatonism of this period seems exceedingly superstitious and obscurantist in comparison to the high minded ethics of the Stoics, the hard-headed materialism of the Epicureans or the paradigmatic simplicity of the Skeptics.

3 – Both were termed “The Great.” Remember, the Church not only passed on the much of the classical corpus but also the words that frame the memory of the past.

4 – The Roman Catholic Church has no doctrinally dictated position on human evolution, but operationally its intellectual elite and priestly class have made their peace with the grosser features of descent with modification.

5 – People forget there were several “Reformations.” The Lutheran Reformation was surpassed by the Reformed Reformation (the genius of Calvin was the driving force behind this), but in the end the apex of Reforming zeal was encapsulated in the maelstrom of the Radical Reformation which birthed not only conventional sects like the Baptists, but also modern day theological heretics like the Unitarians or strange antinomian cultists like the Levellers.

6 – In the late 4th century St. Ambrose made Theodosius repent of the slaughter of Thessolanicans who had killed his officials. One thing left out of many of the stories is that the Thessolanicans accused one particular general of engaging in forced homosexual acts against them. The story illustrates that even a Christian Emperor like Theodosius believed there were greater sins than homosexuality in the world, in this case, rebellion against and murder of the hands of his power.

Posted by razib at 02:29 PM

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The hereditary effects of smoking [or neo-Lamarkianism]?

From The Sunday Times:
The study suggests that some of the chemicals in smoke can permanently alter the DNA of those exposed to it in ways that can be inherited by smokers’ children, grandchildren and possibly subsequent generations too.

The researchers analysed asthma rates in both the children and grandchildren of women who smoked during pregnancy.

They found the grandchildren of such women had 2.1 times the normal risk of developing asthma. The children of women who smoked in pregnancy were 1.5 times more likely to develop asthma.

. . .

They found children whose mothers and grandmothers both smoked had the highest risk, with a likelihood of developing asthma 2.6 times higher than normal.

Hat tip: Drudge Report

Download file: “Maternal and Grandmaternal Smoking Patterns Are Associated With Early Childhood Asthma” from the April 2005 edition of Chest

Posted by Arcane at 04:24 PM

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Question of the day

What makes a Firefly’s tail glow?

(I’m pretty sure Razib knows the answer, so I’ll ask him to sit this one out)

UPDATE OK That one was easy and AG got it in the comments, so I’ll ask a second question: why is complete COX-2 inhibition not a good thing? (COX-2 is the protein implicated in colon, breast and prostate cancer for which drugs such as Vioxx inhibit)

Posted by scottm at 10:51 AM

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Tales from the blank slate – Part II

Striking another body blow against Discrimination, the Swedish government has now decided to ban all gender-based differential pricing. Women will have to pay full price for a number of services, such as Taxi rides, and will no longer be let into nightclubs at earlier ages than males.

Males will on the other hand no longer be able to enjoy cut-rate haircuts. Take that patriarchy!

This bold initiative comes shortly after the latest government equality push, aimed at making it harder for women to stay at home with their children. (Essentially, unless you split parental leave 50-50, you will be punished financially)

TangoMan Adds: Let’s not overlook the recent turn of events in Norway where the government will dissolve a company that doesn’t have women comprising 40% of its Board of Directors.

Posted by dobeln at 03:07 AM

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Code of many colors

Can researchers see race in the genome? (Science News). Like many popular press articles the link (which is the first in a two part series, the second to be titled “The Race to Prescribe”) is presented in the format of “the other side disagrees….” This is a shift, as the assumption is now that there are two valid sides. For the sake of argument, if the scientific consensus does start shifting toward the relevance of populational information presented as clusters (“race”), the expositors better get ready to beat back a resurgence of Platonic typologies. The fact is that the public does not usually engage in “population thinking” as biologists have been wont to do since the dominance of the Modern Synthesis even when it comes to the general fact of evolution. Remember, this is the public that credulously soaks up headlines shouting that “the gene has been discovered that causes-an-extremely-complex-polygenic trait-modified by many environmental factors” (fine print: “scientists note that gene X accounts for 15% of the variation in trait Y”).

Related: Pattern Classification in Population Genetics, Pt. 1. Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies. Evidence for Gradients of Human Genetic Diversity Within and Among Continents.

Posted by razib at 10:57 PM

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