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Let him languish in pain crying aloud for mercy, and let there be no surceaseto his agony till he sing in dissolution. Let bookworms gnaw his entrails in token of the Worm. Even a worldly skeptic, with a strong craving for what he had in his hands, might have hesitatedbefore slipping such a book into his cloak.

If the monks were poor or perhaps simply venal, they could be offered some money to partwith their books, but the very interest showed by a stranger would inevitably make the price soar. Itwas always possible to ask the abbot to allow a manuscript to be carried off, with a solemn promisethat it would be shortly returned.

But though exceptionally trusting or naive abbots existed, they werefew and far between. The re was no way to compel assent, and if the answer was no, the wholeventure was a dead loss. As a last resort, one could always defy curses and try theft, of course, butmonastic communities were cultures of surveillance. Visitors would be watched particularlycarefully, the gates were shut and locked at night, and some of the brothers were stout churls whowould not scruple to beat an apprehended thief to within an inch of his life.

Poggio was almost uniquely suited to meet these challenges. He had been exceptionally welltrained in the special skills needed to decipher old handwriting. He was a wonderfully gifted Latinist,with a particularly acute eye for the telltale diction, rhetorical devices, and grammatical structures ofclassical Latin.

He had read widely and attentively in the literature of antiquity and had committed tohis capacious memory the dozens of clues that hinted at the identity of particular authors or works thathad been lost. He was not himself a monk or a priest, but his long service in the papal curia or courthad given him intimate, inside knowledge of the institutional structures of the Church, as well aspersonal acquaintance with many of its most powerful clerics, including a succession of popes.

He was amarvelous raconteur, a sly gossip, and an indefatigable teller of jokes, many of them off-color. Hecould not, to be sure, converse with the German monks in their native language. Though he had livedfor more than three years in a German-speaking city, by his own account he had learned no German. For so gifted a linguist, this ignorance seems to have been willed: German was the language of thebarbarians, and Poggio evidently had no interest in acquiring it.

In Constance he probably cocoonedhimself almost entirely in a Latin- and Italian-speaking social world. But if a failure to speak German must have been vexing on the road, at inns or other waystations, it would not have posed a serious problem once Poggio had arrived at his destination. The abbot, the librarian, and many other members of the monastic community would have spoken Latin.

The y would not in all likelihood have possessed the elegant classical Latin that Poggio hadpainstakingly mastered but rather, to judge from the many vigorous contemporary literary works thatsurvive, a vital, fluent, highly flexible Latin that could swoop effortlessly from the subtlest ofscholastic distinctions to the earthiest of obscenities. If Poggio sensed that he could impress his hostswith moral seriousness, he could have discoursed eloquently about the miseries of the humancondition; if he thought he could win them over by making them laugh, he could have launched intoone of his tales of foolish rustics, compliant housewives, and sexually rapacious priests.

Poggio possessed one further gift that set him apart from virtually all the other book-huntinghumanists. He was a superbly well-trained scribe, with exceptionally fine handwriting, great powersof concentration, and a high degree of accuracy. It is difficult for us, at this distance, to take in the.

That typeface was based on the beautiful handwriting 13 ofPoggio and his humanist friends. What Poggio did by hand to produce a single copy would soon bedone mechanically to produce hundreds. But this achievement lay in the future, and, in any case, the printers who set the books in typestill depended on accurate, readable, handwritten transcriptions, often of manuscripts that wereillegible to all but a few.

What this meant was that he could not only inveigle his wayinto the monastery and nose out the precious manuscripts of lost works, but also that he could borrowthem, copy them quickly, and send the results back to humanists waiting eagerly at home in Italy. Ifborrowing proved impossible—that is, if the librarian refused to lend a particular manuscript—Poggio could copy it on the spot, or, if necessary, could entrust the task to a scribe whom he hadpersonally trained up to at least a minimal level of competence.

In , then, Poggio the book hunter had a near-perfect conjunction of time, skills, and desire. Allthat he lacked was ready money. Traveling, even frugally, was expensive. The re were costs forrenting a horse; fees for crossing rivers or riding on toll roads; charges, little more than extortion, bysurly customs officials and agents of petty lordlings; gratuities to guides through difficult passes; and,of course, bills for food and lodging and stabling at inns.

He also needed money to pay an assistantscribe, and to provide, if necessary, the incentive to induce a reluctant monastery to lend its treasure. Even if he had banked some funds from his years in the papal bureaucracy, Poggio is veryunlikely to have been able to pay these costs on his own.

In such circumstances, the inveterate letterwriter would have had recourse to his pen. It is probable that he wrote to wealthy friends at homewho shared his passion and explained to them that circumstances had suddenly given him theopportunity about which they had only dreamed.

In good health, untrammeled by work or family,obliged to no one, at liberty to come and go as he chose, he was prepared to embark on a serioussearch for the lost treasures that meant most to them—the heritage of the ancient world. Such support, whether it came from a single rich patron or from a group of fellow humanists,helps to account for the fact that in January , Poggio was heading toward the destination wherehe would make his discovery. The support must have been considerable, for this was not his onlybook-hunting expedition that winter.

It followed directly on another trip, to the venerable monasteryof St. Gall, not far from the city of Constance, and that trip was itself a return visit. The precedingyear at St. Gall, in the company of two Italian friends, Poggio had made a series of important finds. Thinking that they might have overlooked other treasures, he and one of the friends went back. Poggio and his companion, Bartolomeo de Aragazzi, had much in common. Both hailed fromTuscany, Poggio from the modest town of Terranuova near Arezzo, Bartolomeo from the beautifulhilltop city of Montepulciano.

Both had gone to Rome and had acquired positions as scriptors in thepapal curia. And both were ardent humanists, eager to use their skills inreading and copying to recover the lost texts of antiquity. The y were close friends, working and traveling together and sharing the same ambition, butthey were also rivals, competitors in the pursuit of the fame that came with discovery.

Not only were both booksexceedingly minor but also, as Bartolomeo himself must have known, both were already available inItaly, so in fact neither was actually a discovery. In late January, having failed to lay hands on the great treasures they had hoped to uncover andperhaps feeling the burden of their competitiveness, the friends went their separate ways.

Poggioevidently headed north, probably accompanied by a German scribe whom he was training. Bartolomeo seems to have gone off by himself. He planned then to go on to still more remotemonasteries. Gall and wasforced to return to Constance, where it took him months to recuperate. Poggio, on the road north,would not have known that, since Bartolomeo had dropped out of the hunt, he was now searchingalone. Poggio did not like monks. He knew several impressive ones, men of great moral seriousness andlearning.

But on the whole he found them superstitious, ignorant, and hopelessly lazy. Monasteries, hethought, were the dumping grounds for those deemed unfit for life in the world. Noblemen fobbed offthe sons they judged to be weaklings, misfits, or good-for-nothings; merchants sent their dim-witted orparalytic children there; peasants got rid of extra mouths they could not feed. The hardiest of theinmates could at least do some productive labor in the monastery gardens and the adjacent fields, asmonks in earlier, most austere times had done, but for the most part, Poggio thought, they were a packof idlers.

The Churchwas a landlord, wealthier than the greatest nobles in the realm, and it possessed the worldly power toenforce its rents and all its other rights and privileges. When the newly elected bishop of Hildesheim,in the north of Germany, asked to see the diocesan library, he was brought to the armory 17 and shownthe pikes and battleaxes hanging on the walls; these, he was informed, were the books with which therights of the bishopric had been won and must be defended.

The inhabitants of wealthy monasteriesmight not have to call upon these weapons very frequently, but, as they sat in the dim light andcontemplated their revenues, they knew—and their tenants knew—that brute force was available. With his friends in the curia Poggio shared jokes about the venality, stupidity, and sexualappetite of monks.

This is no doubtan extraordinary proof of merit, that they sit up to exercise themselves in psalmody. What would theysay if they rose to go to the plough, like farmers, exposed to the wind and rain, with bare feet, andwith their bodies thinly clad? But, of course, as he approached his targeted monastery, Poggio would have buried theseviews in his breast.

He may have despised monastic life, but he understood it well. He knewprecisely where in the monastery he needed to go and what ingratiating words he had to speak to gainaccess to the things he most wanted to see. Above all, he knew exactly how the things he sought hadbeen produced.

Though he ridiculed what he regarded as monastic sloth, he knew that whatever hehoped to find existed only because of centuries of institutional commitment and long, painstakinghuman labor. The Benedictine Rule had called for manual labor, as well as prayer and reading, and it wasalways assumed that this labor could include writing. The early founders of monastic orders did notregard copying manuscripts as an exalted activity; on the contrary, as they were highly aware, most ofthe copying in the ancient world had been done by educated slaves.

The task was therefore inherentlyhumiliating as well as tedious, a perfect combination for the ascetic project of disciplining the spirit. Poggio had no sympathy with such spiritual discipline; competitive and ambitious, his spirit longed toshine in the light of the world, not to shrink from its gaze. For him copying manuscripts, which he didwith unrivalled skill, was not an ascetic but rather an aesthetic undertaking, one by which headvanced his own personal reputation.

But by virtue of that skill he was able to see at a glance—witheither admiration or scorn—exactly what effort and ability had gone into the manuscript that lay. Not every monk was equally adept at copying, just as not every monk was equally adept at thehard farm labor on which the survival of the early communities depended. The early regulationsalready envisaged a division of labor, as in the Rule of St.

Those who wrote unusually well—in fine, clear handwriting that the othermonks could easily read and with painstaking accuracy in the transcription—came to be valued. The high price, at a time when life was cheap, suggests both how important and how difficult itwas for monasteries to obtain the books that they needed in order to enforce the reading rule. Even themost celebrated monastic libraries of the Middle Ages were tiny in comparison with the libraries ofantiquity or those that existed in Baghdad or Cairo.

To assemble a modest number of books, in thelong centuries before the invention of the printing press forever changed the equation, meant theeventual establishment of what were called scriptoria, workshops where monks would be trained tosit for long hours making copies.

At first the copying was probably done in an improvised setting inthe cloister, where, even if the cold sometimes stiffened the fingers, at least the light would be good. But in time special rooms were designated or built for the purpose. In the greatest monasteries,increasingly eager to amass prestigious collections of books, these were large rooms equipped withclear glass windows under which the monks, as many as thirty of them, sat at individual desks,sometimes partitioned off from one another.

Those tools also included rulers, awls to make tiny holes for ruling the lines evenly , fine-pointed metal pens for drawing the lines, readingframes to hold the book to be copied, weights to keep the pages from turning. For manuscripts thatwere to be illuminated, there were still other specialized tools and materials. Most books in the ancient world took the form of scrolls—like the Torah scrolls that Jews usein their services to this day—but by the fourth century Christians had almost completely opted for adifferent format, the codex, from which our familiar books derive.

The codex has the huge advantageof being far easier for readers to find their way about in: the text can be conveniently paginated andindexed, and the pages can be turned quickly to the desired place. Since papyrus was no longer available and paper did not come into general use until the.

The se surfaces needed to bemade smooth, and hence another tool that the monastic librarian distributed was pumice stone, to rubaway the remaining animal hair along with any bumps or imperfections. And the best of the lot was uterine vellum,from the skins of aborted calves.

Brilliantly white, smooth, and durable, these skins were reservedfor the most precious books, ones graced with elaborate, gemlike miniatures and occasionallyencased in covers encrusted with actual gems. The libraries of the world still preserve a reasonablenumber of these remarkable objects, the achievement of scribes who lived seven or eight hundredyears ago and labored for untold hours to create something beautiful.

Good scribes were exempted from certain times of collective prayer, in order to maximize thehours of daylight in the scriptorium. And they did not have to work at night: because of an entirelyjustifiable fear of fire, all candlelight was forbidden. But for the time—about six hours a day—thatthey actually spent at their desks, their lives belonged entirely to their books. Indeed, insofar as the copying was a form ofdiscipline—an exercise in humility and a willing embrace of pain—distaste or simpleincomprehension might be preferable to engagement.

Curiosity was to be avoided at all costs. But he understood that his passionate hope of recovering reasonablyaccurate traces of the ancient past depended heavily on this subordination. An engaged reader, Poggioknew, was prone to alter his text in order to get it to make sense, but such alterations, over centuries,inevitably led to wholesale corruptions.

It was better that monastic scribes had been forced to copyeverything exactly at it appeared before their eyes, even those things that made no sense at all. A sheet with a cutout window generally covered the page of the manuscript being copied, sothat the monk had to focus on one line at a time. And monks were strictly forbidden to change whatthey thought were mistakes in the texts they were copying. The y could correct only their own slips ofthe pen by carefully scraping off the ink with a razor and repairing the spot with a mixture of milk,cheese, and lime, the medieval version of our own product for whiting out mistakes.

The re was nocrumpling up the page and starting afresh. Though the skins of sheep and goats were plentiful, theprocess of producing parchment from them was laborious. Good parchment was far too valuable andscarce to be discarded. This value helps to account for the fact that monasteries collected ancient.

To be sure, there were a certain number of abbots and of monastic librarians who treasurednot only the parchment but also the pagan works written on them. Steeped in classical literature, somebelieved that they could rifle its treasures without contamination, the way the ancient Hebrews hadbeen permitted by God to steal the riches of the Egyptians. But over the generations, as a substantialChristian literature was created, it became less easy to make such an argument.

Fewer and fewermonks were inclined, in any case, to make it. Between the sixth century and the middle of the eighthcentury, Greek and Latin classics virtually ceased to be copied at all. What had begun as an activecampaign to forget—a pious attack on pagan ideas—had evolved into actual forgetting. The y had been reduced to the conditionof mute things, sheets of parchment, stitched together, covered with unread words. Only the remarkable durability of the parchment used in these codices kept the ideas of theancients alive at all, and, as the humanist book hunters knew, even strong material was no guaranteeof survival.

Working with knives, 22 brushes, and rags, monks often carefully washed away the oldwritings—Virgil, Ovid, Cicero, Seneca, Lucretius—and wrote in their place the texts that they wereinstructed by their superiors to copy. The task must have been a tiresome one, and, for the very rarescribe who actually cared about the work he was erasing, an excruciating one.

But no medieval monk would have been encouraged to read, as it were, betweenthe lines. The monastery was a place of rules, but in the scriptorium there were rules within rules. Access was denied to all non-scribes. Absolute silence reigned. Scribes were not allowed to choosethe particular books that they copied or to break the dead silence by requesting aloud from thelibrarian such books as they might wish to consult in order to complete the task that had been assignedthem.

An elaborate gestural language was invented in order to facilitate such requests as werepermitted. If a scribe wanted to consult a psalter, he made the general sign for a book—extending hishands and turning over imaginary pages—and then, by putting his hands on his head in the shape of acrown, the specific sign for the psalms of King David. If he was asking for a pagan book, he began,after making the general sign, to scratch behind his ear, like a dog scratching his fleas.

And if hewished to have what the Church regarded as a particularly offensive or dangerous pagan book, hecould put two fingers into his mouth, as if he were gagging. Poggio was a layman, part of a very different world. His precise destination in , after he partedways with Bartolomeo, is not known—perhaps like a prospector hiding the location of his mine, hedeliberately withheld its name from his letters.

The re were dozens of monasteries to which he mighthave gone in the hope of turning up something remarkable, but many scholars have long thought thatthe likeliest candidate is the Benedictine Abbey of Fulda. If it was Fulda that he approached, Poggio could not afford to seem overbearing. Founded inthe eighth century by a disciple of the Apostle of Germany, St. Boniface, the abbey was unusuallyindependent. Its abbot was a prince of the Holy Roman Empire: when he walked in procession, anarmor-clad knight carried the imperial banner before him, and he had the privilege of sitting at the lefthand of the emperor himself.

Many of the monks were German nobles—men who would have had avery clear sense of the respect that was due to them. If the monastery had lost some of the prestige itonce enjoyed and had been forced in the not too distant past to part with some of its immenseterritories, it nonetheless was a force to reckon with.

With his modest birth and very limited means,Poggio, the former apostolic secretary of a disgraced and deposed pope, had few cards to play. From the outside Fuldaresembled a fortress; indeed, in the preceding century, in a bitter dispute with the burghers of theadjacent city, it had been violently attacked.

Inside, like most monasteries, it was strikingly selfsufficient. By January the extensive vegetable, flower, and botanical gardens were in their wintersleep, but the monks would have carefully harvested what they could store for the long, dark months,taking special care to gather the medicinal herbs that would be used in the infirmary and thecommunal bath. The granaries at this point in the winter would have still been reasonably full, andthere would have been ample straw and oats for the horses and donkeys in the stables.

Lookingaround, Poggio would have taken in the chicken coops, the covered yard for sheep, the cowshed withits smell of manure and fresh milk, and the large pigsties. He might have felt a pang for the olives andthe wine of Tuscany, but he knew that he would not go hungry. Aftergreeting him humbly, explaining something about himself, and presenting a letter of recommendationfrom a well-known cardinal, Poggio would almost certainly have begun by expressing his interest inglimpsing the precious relics of St.

Boniface and saying a prayer in their holy presence. His life, afterall, was full of such observances: bureaucrats in the papal court routinely began and ended their dayswith prayers. The visitor would then as a special favor have been led into the basilica. The vast St. The re by candlelight, enshrined in a rich setting of gold,crystal, and jewels, he would have seen the bones of the saint, massacred in by the Frisians hewas struggling to convert.

When he and his hosts emerged once again into the light and when he deemed that he hadreached the appropriate moment, Poggio would have nudged the conversation toward his actualpurpose in coming. Rabanus Maurus was a prolific author of biblical commentaries, doctrinal treatises, pedagogicalguides, scholarly compendia, and a series of fantastically beautiful poems in cipher.

Most of theseworks Poggio could easily have seen in the Vatican Library, along with the vast tome for whichRabanus was best known: a work of stupefying erudition and dullness that attempted to bring togetherin its twenty-two books all of human knowledge. As all schools do, the one at Fulda needed books, andRabanus had met the need by greatly enriching the monastic library.

Rabanus, who as a young man 24had studied with Alcuin, the greatest scholar of the age of Charlemagne, knew where to get his handson important manuscripts. He had them brought to Fulda, where he trained a large cohort of scribes tocopy them. And so he had built what was for the time a stupendous collection. It was far enough into the past to hold out the possibility of a link to a more distantpast. Who knew what was sitting on those shelves, untouched perhaps forcenturies?

Tattered manuscripts that had chanced to survive the long nightmare of chaos anddestruction, in the wake of the fall of the Roman Empire, might well have found their way to remoteFulda. The volume was a catalogue, and as he pored over its pages, Poggio pointed—for the rule of silence inthe library was strictly observed—to the books he wanted to see. Genuine interest, as well as a sense of discretion, might have dictated that Poggio request firstto see unfamiliar works by one of the greatest Church Fathers, Tertullian.

The n, as the manuscriptswere brought to his desk, he plunged, with what must have been increasing excitement, into a series ofancient Roman authors whose works were utterly unknown to him and to any of his fellow humanists. Though Poggio did not reveal precisely where he went, he did reveal—indeed, he trumpeted—whathe had found. For what all book hunters dreamed of was actually happening. He opened an epic poem in some 14, lines on the wars between Rome and Carthage.

Poggio might have recognized the name of the author, Silius Italicus, though until this moment none of. A canny politician and a wily, unscrupulous orator, who served as a tool in asuccession of show trials, Silius had managed to survive the murderous reigns of Caligula, Nero, andDomitian.

He opened another long poem, this one by an author, Manilius, whose name the book hunterwould certainly not have recognized, for it is not mentioned by any surviving ancient author. More ghosts surged up from the Roman past.

Yet anothermanuscript was a discovery whose thrill might have been tinged for him with melancholy: a largefragment of a hitherto unknown history of the Roman Empire written by a high-ranking officer in theimperial army, Ammianus Marcellinus. A clearheaded, thoughtful, and unusually impartial historian,Ammianus seems to have sensed the impending end. Even the smallest of the finds that Poggio was making was highly significant—for anything atall to surface after so long seemed miraculous—but they were all eclipsed, from our own perspectiveif not immediately, by the discovery of a work still more ancient than any of the others that he hadfound.

One of the manuscripts consisted of a long text written around 50 BCE by a poet andphilosopher named Titus Lucretius Carus. Poggio would almost certainly have recognized the name Lucretius from Ovid, Cicero, andother ancient sources he had painstakingly pored over, in the company of his humanist friends, butneither he nor anyone in his circle 26 had encountered more than a scrap or two of his actual writing,which had, as far as anyone knew, been lost forever.

Poggio may not have had time, in the gathering darkness of the monastic library, and under thewary eyes of the abbot or his librarian, to do more than read the opening lines. Ordering his scribe tomake a copy, he hurried to liberate it from the monastery. What is not clear is whether he had anyintimation at all that he was releasing a book that would help in time to dismantle his entire world.

Italian humanists, on the lookout for clues to lost ancient works, would have beenalert to even fleeting references in the works of those celebrated authors whose writings had survivedin significant quantities. The conjunction was as rare then as it is now.

Cicero and his brother were not alone in grasping that Lucretius had accomplished a nearperfectintegration of intellectual distinction and aesthetic mastery. The greatest Roman poet, Virgil,about fifteen years old when Lucretius died, was under the spell of On the Nature of Things. But Virgil did not mention 4 his hero by name,and, though he had certainly read the Georgics, Poggio was unlikely to have picked up the allusionbefore he had actually read Lucretius.

Many of the major poets and philosophers of ancient Rome had been celebrities in their owntime, the objects of gossip which eager book hunters centuries later pored over for clues. But in thecase of Lucretius there were almost no biographical traces. The poet must have been a very private. That work, difficult and challenging, was hardly the kind of popular success that gotdiffused in so many copies that significant fragments of it were assured of surviving into the MiddleAges.

The y were groping in the dark, sensing perhaps a tiny gossamerfilament but unable to track it to its source. And following in their wake, after almost six hundredyears of work by classicists, historians, and archaeologists, we know almost nothing more than theydid about the identity of the author. The Lucretii were an old, distinguished Roman clan—as Poggio may have known—but sinceslaves, when freed, often took the name of the family that had owned them, the author was notnecessarily an aristocrat.

Still, an aristocratic lineage was plausible, for the simple reason thatLucretius addressed his poem, in terms of easy intimacy, to a nobleman, Gaius Memmius. That namePoggio might have encountered in his wide reading, for Memmius had a relatively successful 6political career, was a patron of celebrated writers, including the love poet Catullus, and was himselfreputed to be a poet an obscene one, according to Ovid.

The answer, for Poggio and his circle, would have come almost completely from a briefbiographical sketch that the great Church Father St. Jerome c. After a love-philtre hadturned him mad, and he had written, in the intervals of his insanity, several books which Cicerorevised, he killed himself by his own hand in the forty-fourth year of his age.

But the humanist book hunter waspart of a generation passionately eager to unearth ancient texts, even by those whose lives epitomizedmoral confusion and mortal sin. And the thought that Cicero himself had revised the books wouldhave sufficed to quiet any lingering reservations. As a person, Lucretius remains almost 8 as little known ashe was when Poggio recovered his poem in The discoveries were made possible by a famous ancient disaster.

Buried under some sixty-five feet of volcanicdebris hardened to the density of concrete, this site, where wealthy Romans had once vacationed intheir elegant, colonnaded villas, was forgotten until the early eighteenth century, when workmen,digging a well, uncovered some marble statues. An Austrian officer—for Naples at the time wasunder the control of Austria—took over, and excavators began digging shafts through the thick crust. The explorations, which continued when Naples passed into Bourbon hands, were extremelycrude, less an archaeological investigation than a prolonged smash-and-grab.

The official in chargefor more than a decade was a Spanish army engineer, Roque Joaquin de Alcubierre, who seemed totreat the site as an ossified garbage dump in which loot had unaccountably been buried. In , under a new director, the explorers became somewhat more careful about what theywere doing.

Others thoughtthat the peculiar fragments might have been rolls of burned cloth or fishing nets. The n one of theseobjects, chancing to fall on the ground, broke open. The unexpected sight of letters inside what hadlooked like a charred root made the explorers realize what they were looking at: books. The y hadstumbled on the remains of a private library. The volumes that Romans piled up in their libraries were smaller than most modern books:they were for the most part written on scrolls of papyrus.

The reeds were harvested; their stalks cut open and sliced into very thinstrips. The strips were laid side by side, slightly overlapping one another; another layer was placedon top, at right angles to the one below; and then the sheet was gently pounded with a mallet.

The natural sap that was released allowed the fibers to adhere smoothly to each other, and the individualsheets were then glued into rolls. Small landowners in Egypt had long realized that they could write their tax receipts on a. Priests could use this medium to record the precise language forsupplicating the gods; poets could lay claim to the symbolic immortality they dreamed of in their art;philosophers could convey their thoughts to disciples yet unborn.

Romans, like the Greeks beforethem, easily grasped that this was the best writing material available, and they imported it in bulkfrom Egypt to meet their growing desire for record keeping, official documents, personal letters, andbooks. A roll of papyrus might last three hundred years. The room unearthed 12 in Herculaneum had once been lined with inlaid wooden shelves; at itscenter were the traces of what had been a large, freestanding, rectangular bookcase.

Scattered aboutwere the carbonized remains—so fragile that they fell apart at the touch—of the erasable waxedtablets on which readers once took notes a bit like the Mystic Writing Pads with which children playtoday. The shelves had been piled high with papyrus rolls. Some of the rolls, perhaps the morevaluable ones, were wrapped about with tree bark and covered with pieces of wood at each end. Inanother part of the villa, other rolls, now fused into a single mass by the volcanic ash, seemed to havebeen hastily bundled together in a wooden box, as if someone on the terrible August day had for abrief, wild moment thought to carry some particularly valued books away from the holocaust.

Altogether—even with the irrevocable loss of the many that were trashed before it was understoodwhat they were—some eleven hundred books were eventually recovered. Many of the rolls in what became known as the Villa of the Papyri had been crushed by fallingdebris and the weight of the heavy mud; all had been carbonized by the volcanic lava, ash, and gas.

But what had blackened these books had also preserved them from further decay. For centuries theyhad in effect been sealed in an airtight container. Even today only one small segment of the villa hasbeen exposed to view, and a substantial portion remains unexcavated.

The discoverers, however,were disappointed: they could barely make out anything written on the charcoal-like rolls. And whenagain and again they tried to unwind them, the rolls inevitably crumbled into fragments. Dozens, perhaps hundreds, of books were destroyed in these attempts. But eventually a numberof the rolls that had been cut open were found to contain near the center some readable portions.

Atthis point—after two years of more or less destructive and fruitless effort—a learned Neapolitanpriest who had been working in the Vatican Library in Rome, Father Antonio Piaggio, was called in. Taking issue with the prevailing method of investigation—simply scraping off the charred outerlayers of the rolls until some words could be discerned—he invented an ingenious device, a machinethat would delicately and slowly unroll the carbonized papyrus scrolls, disclosing much morereadable material than anyone had imagined to have survived.

The researchers were disappointed—they had been hoping to find lost works by the likes of Sophocles and Virgil—but what they had soimplausibly snatched from oblivion has an important bearing on the discovery made centuries earlierby Poggio. Why were the works of a minor Greek philosopher in the library of the elegant seaside retreat?

And why, for that matter, did a vacation house have an extensive library at all? Philodemus, a. That moment was theculmination of a lengthy process that braided together Greek and Roman high culture. The two cultures had not always been comfortably intertwined. Among the Greeks, Romanshad long held the reputation of tough, disciplined people, with a gift for survival and a hunger forconquest.

When their independent city-states were still flourishing, Greek intellectuals collected some arcanelore about the Romans, as they did about the Carthaginians and Indians, but they did not find anythingin Roman cultural life worthy of their notice. The Romans of the early republic might not altogether have disagreed with this assessment. Rome had traditionally been wary of poets and philosophers. It prided itself on being 13 a city ofvirtue and action, not of flowery words, intellectual speculation, and books.

Skeptical as ever of effete intellectuals and priding themselveson their practical intelligence, Romans nonetheless acknowledged with growing enthusiasm theachievements of Greek philosophers, scientists, writers, and artists. The y made fun of what they tookto be the defects of the Greek character, mocking what they saw as its loquaciousness, its taste forphilosophizing, and its foppishness. But ambitious Roman families sent their sons to study at thephilosophical academies for which Athens was famous, and Greek intellectuals like Philodemus werebrought to Rome and paid handsome salaries to teach.

It was never quite respectable for a Roman aristocrat to admit to a boundlessly ardentHellenism. Yet Roman temples and public spaces were graced with splendidstatues stolen from the conquered cities of the Greek mainland and the Peloponnese, while battlehardenedRoman generals adorned their villas with precious Greek vases and sculptures.

The survival of stone and fired clay makes it easy for us to register the pervasive presence inRome of Greek artifacts, but it was books that carried the full weight of cultural influence. Perseus and his three sons weresent in chains to be paraded through the streets of Rome behind the triumphal chariot. In the traditionof national kleptocracy, Aemilius Paulus shipped back enormous plunder to deposit in the Romantreasury.

It became increasingly fashionable for wealthyRomans to amass large private libraries in their town houses and country villas. The re were nobookshops in the early years in Rome, but, in addition to the collections seized as booty, books couldbe purchased from dealers in southern Italy and Sicily where the Greeks had founded such cities asNaples, Tarentum, and Syracuse.

The grammarian Tyrannion is reputed to have had 30, volumes;. Rome had caught the Greek fever forbooks. Lucretius lived his life in a culture of wealthy private book collectors, and the society intowhich he launched his poem was poised to expand the circle of reading to a larger public.

The idea seems to have originated with Julius Caesar, who admired the publiclibraries he had seen in Greece, Asia Minor, and Egypt, and determined to bestow such an institutionupon the Roman people. But Caesar was assassinated before he could carry out the plan, and it tookPollio, who had sided with Caesar against Pompey and then with Mark Antony against Brutus, to doso.

A skillful military commander, canny or extremely lucky in his choice of allies, Pollio was alsoa man of broad literary interests. Apart from a few fragments of his speeches, all of his writings arenow lost, but he composed tragedies—worthy of Sophocles, according to Virgil—histories, andliterary criticism, and he was one of the first Roman authors to recite his writings to an audience ofhis friends.

The library established by Pollio 16 was built on the Aventine Hill and paid for, in the typicalRoman way, by wealth seized from the conquered—in this case, from a people on the Adriatic coastwho had made the mistake of backing Brutus against Antony. Shortly afterwards, the emperorAugustus founded two more public libraries, and many subsequent emperors followed in his wake.

Altogether, by the fourth century CE, there were twenty-eight public libraries in Rome. The structures, all of which have been destroyed, evidently followed the same general pattern, one thatwould be familiar to us. The re was a large reading room adjoining smaller rooms in which thecollections were stored in numbered bookcases. The reading room, either rectangular or semicircularin shape and sometimes lit through a circular opening in the roof, was adorned with busts or life-sizedstatues of celebrated writers: Homer, Plato, Aristotle, Epicurus, among others.

The statuesfunctioned, as they do for us, as an honorific, a gesture toward the canon of writers whom everycivilized person should know. But in Rome they may have had an additional significance, akin to themasks of ancestors that Romans traditionally kept in their houses and that they donned oncommemorative occasions.

That is, they were signs of access to the spirits of the dead, symbols of thespirits that the books enabled readers to conjure up. Many other cities 17 of the ancient world came to boast public collections, endowed by taxrevenues or by the gifts of wealthy, civic-minded donors.

Greek libraries had had few amenities, butthroughout their territories the Romans 18 designed comfortable chairs and tables where readers couldsit and slowly unfold the papyrus, the left hand rolling up each column after it was read. The greatarchitect Vitruvius—one of the ancient writers whose work Poggio recovered—advised that librariesshould face toward the east, to catch the morning light and reduce the humidity that might damagebooks.

Excavations at Pompeii and elsewhere have uncovered the plaques honoring the donors, alongwith statuary, writing tables, shelves to store papyrus rolls, numbered bookcases to hold the boundparchment volumes or codices that gradually began to supplement the rolls, and even graffitiscribbled on the walls.

The resemblance to the design of public libraries in our own society is noaccident: our sense that a library is a public good and our idea of what such a place should look likederive precisely from a model created in Rome several thousand years ago. Papyrus rolls were carefully indexed, labeled with a protruding tag called inGreek a sillybos , and stacked on shelves or stored in leather baskets. Even in the elaborate bathcomplexes that Romans loved, reading rooms, decorated with busts of Greek and Latin authors, werecarefully designed to make it possible for educated Romans to combine care for the body with carefor the mind.

This broad commitment to reading, with its roots in the everyday lives of the Roman eliteover many generations, explains why a pleasure palace like the Villa of the Papyri had a well-stockedlibrary. In the s, modern archaeologists resumed serious work on the buried villa, in the hopes of gaininga better understanding of the whole style of life expressed in its design, a design vividly evoked in thearchitecture of the Getty Museum in Malibu, California, where some of the statues and other treasuresfound at Herculaneum now reside.

The bulk of the marble and bronze masterpieces—images of godsand goddesses, portrait busts of philosophers, orators, poets, and playwrights; a graceful youngathlete; a wild boar in mid-leap; a drunken satyr; a sleeping satyr; and a startlingly obscene Pan andgoat in flagrante delicto—are now in the National Museum in Naples.

The renewed exploration got off to a slow start: the rich volcanic soil covering the site wasused to grow carnations, and the owners were understandably reluctant to permit excavators todisrupt their business. But after lengthy negotiations, researchers were permitted to descend the shaftsand approach the villa in small gondolalike craft that could glide safely through tunnels that had beenbored through the ruins. Traces of vine shoots and leaves enabled them to determine the precisesite of the garden where some two thousand years ago the wealthy proprietor and his cultivatedfriends once came together.

It is, of course, impossible at this great distance in time to know exactly what these particularpeople talked about, during the long sunlit afternoons in the colonnaded garden at Herculaneum, butan intriguing further clue turned up, also in the s. Scholars, this time above ground, were at workonce again on the blackened papyri that had been discovered by the eighteenth-century treasurehunters.

The se scrolls, hardened into lumps, had resisted the early attempts to open them and had sat. In , using new techniques,Tommaso Starace managed to open two badly preserved papyri. He mounted the legible fragmentsfrom these books—unread since the ancient volcanic eruption—on Japanese paper, microphotographedthem, and undertook to decipher the contents. WhatKleve and his colleagues had found were only sixteen minuscule fragments—little more than wordsor parts of words—that, under close analysis, could be shown to come from books 1, 3, 4, and 5 ofthe six-book-long Latin poem.

Forlorn pieces from an enormous jigsaw puzzle, the fragments bythemselves are virtually meaningless. But their range suggests that the whole of De rerum natura wasin the library, and the presence of that poem in the Villa of the Papyri is tantalizing. The discoveries at Herculaneum enable us to glimpse the social circles where the poem thatPoggio found in the monastic library had originally circulated.

In Herculaneum, it was a native. Piso is known to have had a personal acquaintance with Philodemus. If you will miss uddersand Bromian wine mis en bouteilles in Chios,yet you will see faithful comrades, yet you will hear things far sweeterthan the land of the Phaeacians.

And if you ever turn your eye our way too, Piso, instead of a modestTwentieth we shall lead a richer one. Rome had been afflicted for yearsby political and social unrest, culminating in several vicious civil wars, and though the violence hadabated, the threats to peace and stability were by no means safely past.

Ambitious generalsrelentlessly jockeyed for position; murmuring troops had to be paid in cash and land; the provinceswere restive, and rumors of trouble in Egypt had already caused grain prices to soar. But cosseted by slaves, in the comfort and security of the elegant villa, the proprietor and hisguests had the temporary luxury of regarding these menaces as relatively remote, remote enough atleast to allow them to pursue civilized conversations. Romans of the late republic were remarkably tenacious about this privilege, which they clungto in circumstances that would have made others quail and run for cover.

For them it seemed tofunction as a sign that their world was still intact or at least that they were secure in their innermostlives. Like a man who, hearing the distant sound of sirens in the street, sits down at the Bechstein toplay a Beethoven sonata, the men and women in the garden affirmed their urbane security byimmersing themselves in speculative dialogue.

In the years leading up to the assassination of Julius Caesar, philosophical speculation washardly the only available response to social stress. Religious cults originating in far-off places likePersia, Syria, and Palestine began to make their way to the capital, where they aroused wild fears andexpectations, particularly among the plebs.

A handful of the elite—those more insecure or simplycurious—may have attended with something other than contempt to the prophecies from the east,prophecies of a saviour born of obscure parentage who would be brought low, suffer terribly, and yetultimately triumph. But most would have regarded such tales as the over-heated fantasies of a sect ofstiff-necked Jews. Those of a pious disposition would far more likely have gone as supplicants to the templesand chapels to the gods that dotted the fertile landscape.

It was, in any case, a world in which natureseemed saturated with the presence of the divine, on mountaintops and springs, in the thermal ventsthat spewed smoke from a mysterious realm under the earth, in ancient groves of trees on whosebranches the faithful hung colorful cloths. But though the villa in Herculaneum was in close proximityto this intense religious life, it is unlikely that many of those with the sophisticated intellectual tastesreflected in the library joined processions of pious supplicants.

Ancient Greeks and Romans did not share our idealization of isolated geniuses, working aloneto think through the knottiest problems. Such scenes—Descartes in his secret retreat, callingeverything into question, or the excommunicated Spinoza quietly reasoning to himself while grindinglenses—would eventually become our dominant emblem of the life of the mind. But this vision ofproper intellectual pursuits rested on a profound shift in cultural prestige, one that began with the.

Anthony — in the desert or St. Symeon Stylites — perched on his column. Suchfigures, modern scholars have shown, characteristically had in fact bands of followers, and thoughthey lived apart, they often played a significant role in the life of large communities. But the dominantcultural image that they fashioned—or that came to be fashioned around them—was of radicalisolation. Not so the Greeks and Romans. As thinking and writing generally require quiet and a minimumof distraction, their poets and philosophers must have periodically pulled away from the noise andbusiness of the world in order to accomplish what they did.

But the image that they projected wassocial. Poets depicted themselves as shepherds singing to other shepherds; philosophers depictedthemselves engaged in long conversations, often stretching out over several days. The pulling awayfrom the distractions of the everyday world was figured not as a retreat to the solitary cell but as aquiet exchange of words among friends in a garden. And the activity of choice, for cultivated Romans, as for the Greeksbefore them, was discourse.

The re is, Cicero remarked at the beginning of a typical philosophicalwork, a wide diversity of opinion about the most important religious questions. I found him sitting in an alcove, engaged in debate with Gaius Velleius, a Member of theSenate, accounted by the Epicureans as their chief Roman adherent at the time. With them wasQuintus Lucilius Balbus, who was so accomplished a student of Stoicism as to rank with theleading Greek exponents of that system.

Cicero does not want to present his thoughts to his readers as a tract composed after solitaryreflection; he wants to present them as an exchange of views among social and intellectual equals, aconversation in which he himself plays only a small part and in which there will be no clear victor.

The exchange itself, not its finalconclusions, carries much of the meaning. The discussion itself is what most matters, the fact that wecan reason together easily, with a blend of wit and seriousness, never descending into gossip orslander and always allowing room for alternative views. The dialogues Cicero and others wrote were not transcriptions of real exchanges, though thecharacters in them were real, but they were idealized versions of conversations that undoubtedlyoccurred in places like the villa in Herculaneum.

The conversations in that particular setting, to judgefrom the topics of the charred books found in the buried library, touched on music, painting, poetry,the art of public speaking, and other subjects of perennial interest to cultivated Greeks and Romans. The y are likely to have turned as well to more troubling scientific, ethical, and philosophicalquestions: What is the cause of thunder or earthquakes or eclipses—are they signs from the gods, assome claim, or do they have an origin in nature?

How we can understand the world we inhabit? Whatgoals should we be pursuing in our lives? How are good and evil to be defined? What happens to us when we die? Many of the early readers of those works evidently lacked a fixed repertory of beliefs and practicesreinforced by what was said to be the divine will.

The y were men and women whose lives wereunusually free of the dictates of the gods or their priests. Standing alone, as Flaubert puts it, theyfound themselves in the peculiar position of choosing among sharply divergent visions of the nature ofthings and competing strategies for living. Indeed, thewealthy patron with philosophical interests could have wished to meet the author in person. It wouldhave been a small matter to send a few slaves and a litter to carry Lucretius to Herculaneum to jointhe guests.

And therefore it is even remotely possible that, reclining on a couch, Lucretius himselfread aloud from the very manuscript whose fragments survive. If Lucretius had participated in the conversations at the villa, it is clear enough what he wouldhave said.

His own conclusions would not have been inconclusive or tinged with skepticism, in themanner of Cicero. It was only Epicurus, Lucretius wrote, who could cure the miserable condition of the man. This hero—one strikingly atodds with a Roman culture that traditionally prided itself on toughness, pragmatism, and militaryvirtue—was a Greek who triumphed not through the force of arms but through the power of intellect. On the Nature of Things is the work of a disciple who is transmitting ideas that had been developedcenturies earlier.

Many Greek philosophers, including Plato and Aristotle, came from wealthy families andprided themselves on their distinguished ancestry. Epicurus decidedly had no comparable claims. Hisphilosophical enemies, basking in their social superiority, made much of the modesty of hisbackground. He assisted his father in his school for a pittance, they sneered, and used to go roundwith his mother to cottages to read charms.

One of his brothers, they added, was a pander and livedwith a prostitute. This was not a philosopher with whom respectable people should associatethemselves. That Lucretius and many others did more than simply associate themselves with Epicurus—that they celebrated him as godlike in his wisdom and courage—depended not on his socialcredentials but upon what they took to be the saving power of his vision.

The core of this vision maybe traced back to a single incandescent idea: that everything that has ever existed and everything thatwill ever exist is put together out of indestructible building blocks, irreducibly small in size,unimaginably vast in number. The Greeks had a word for these invisible building blocks, things that,as they conceived them, could not be divided any further: atoms.

Other philosophers had competing theories:the core matter of the universe, they argued, was fire or water or air or earth, or some combination ofthese. Others suggested that if you could perceive the smallest particle of a man, you would find aninfinitesimally tiny man; and similarly for a horse, a droplet of water, or a blade of grass. DNA methylation and histone modification are governed by effector proteins named writers, readers and erasers, which respectively add, bind or remove chemical groups Allis and Jenuwein Effects of environmental agents on ncRNA levels are generally investigated by evaluating miR expression.

They are partially complementary to one or more messenger RNA mRNA molecules; each molecule can modulate the expression of many pathways interacting with many mRNAs causing translational inhibition or mRNA destabilization Pillai et al. These patterns determine the epigenetic state of the genome, named epigenome, which varies by cell type and over time as a consequence of the developmental process Reik et al.

Epigenetic marks are usually heritable, allowing for maintenance of cell identity, but can also be reversible, allowing for developmental plasticity Lee et al. Accumulated evidence has shown an association between epigenetic alterations and pathological conditions, including cancer Lehmann ; Herceg et al.

It is unclear what triggers these epigenetic dysregulations; however, emerging evidence indicates that a variety of environmental factors may have an epigenetic impact Cortessis et al. Large amounts of data were collected on this topic, suggesting that epigenetic alterations could represent a pathway by which environmental factors influence disease risks and ageing. In particular, early embryonic development is highly vulnerable to epigenetic changes caused by environmental conditions.

At this stage, global changes in the epigenetic landscape occur and drive cell-fate decisions: stem cells differentiate into different cell lineages, acquiring cell-type-specific epigenetic signatures which are responsible for differential gene expression and specific cell functions. During this process, environmental stressors can affect epigenetic patterns, leading, later in life, to adverse health effects, according to the theory known as developmental origin of health and disease DOHaD Barouki et al.

Many works analysed alterations of epigenetic marks in human cells exposed to various environmental agents. However, none of them focused on the epigenetic effects of the exposure to extremely low-frequency magnetic fields ELF-MFs , which are today an ubiquitous environmental factor. Humans are increasingly exposed to ELF-MFs generated by everyday electrical devices and powerlines; therefore, concerns about potential health risks have been increasing in recent decades.

Since then, various epidemiological and experimental studies have been performed to evaluate the carcinogenicity of ELF-MF exposure Juutilainen et al. Several studies showed that electromagnetic fields can modulate processes that involve epigenetic mechanisms, such as cell commitment Maziarz et al.

Because of these effects, magnetic fields are considered of interest for therapeutic interventions, including repair of tissue injury and development of bone Varani et al. Therefore, the study of the impact of the ELF-MF exposure on epigenetic marks could be useful for both the above aspects: public health protection and therapeutic use. The purpose of the present review is to summarize the results arising from studies that investigated the link between the exposure to ELF-MF and epigenetic alterations and to explore possible future developments.

Only a modest number of studies have been performed up to now to assess effects of ELF-MF exposure on epigenetics. They are very heterogeneous in experimental designs and exposure systems, as summarized in Table 1. Some evidence suggested that ELF-MFs could affect semen quality in animals and humans, causing dysfunction of the male reproductive system Iorio et al. The underlying possible molecular mechanisms remain unknown.

The research question of the three studies reported below, conducted by the same team, was to find out if epigenetic perturbations could play a role in these phenomena. In the first study, Liu et al. To this purpose, starved mouse spermatocyte-derived GC-2 cells were subjected to an exposure of 50 Hz ELF-MF at various magnetic flux densities for 72 h.

Starvation was induced by culturing the cells in serum-free medium for 12 h before the exposure. The evaluation of the global DNA methylation showed that ELF-MF-exposed GC-2 cells acquired aberrant methylation levels, depending on the magnetic flux density used: a decrease at 1 mT and an increase at 2 mT and 3 mT, as compared with the sham-exposed controls, were observed.

Differently, no influence on the expression of DNMT3a was observed. The result was strengthened by DNA methylation chip analysis that showed a number of differentially methylated sites, both hypermethylated and hypomethylated, in the 1-mT and 3-mT-exposed samples as compared with the control group. Gene expression was also evaluated by microarrays and then confirmed and validated by using RT-qPCR: a total of 84 differentially expressed genes in 1-mT-exposed samples and differentially expressed genes in 3-mT-exposed samples were observed as compared with the control group.

In the second study Liu et al. After exposure, miR levels were evaluated using microarray technology. Those miRs whose expression significantly changed, compared with the sham group, are reported in Table 2. The authors applied a network analysis to predict putative miR target genes and their biological functions and found that many of the predicted miR target genes were involved in critical cellular pathways.

In several cases, the effect depended on the magnetic flux density Table 2. In the third study Liu et al. CCND2 is a crucial cell cycle regulatory gene, and its aberrant expression has been reported in several cancer tissues and cell lines Ando et al. To investigate the potential mechanism of the deregulation of miRb-5p, DNA methylation of its host gene CTDSP1 was evaluated, but no significant change was found indicating that it was not involved in the phenomenon.

The authors concluded that the regulation of miRs, and in particular of miRb-5p-CCND2-mediated cell cycle regulation, as well as the alterations of global methylation, related to DNMT altered expression, could play a role in the biological effects of intermittent 50 Hz ELF-MF exposure on spermatocyte-derived cells. However, no hypothesis was formulated about the different responses to different magnetic flux densities.

The research question of the study carried out by Manser et al. Haematopoietic differentiating cells were subjected to genome-wide methylation analysis at single CpG sites. As expected, the pattern of DNA methylation changed dramatically during neutrophilic granulopoiesis, but no significant difference in methylation levels was observed between ELF-MF-exposed and control samples.

Several studies have shown that specific electromagnetic field exposure can inhibit proliferation of cancer cells in vitro and cause decrease of tumour volume and longer survival time in vivo Wang et al. Ren et al. In particular, they focused on miRa, since it is known to be downregulated in several cancer cells, including lung cancer Xue et al.

They used a rotating magnetic field RMF of 7. Differently from the other types of dynamic magnetic fields, the direction of the magnetic field in RMF is constantly changing. This specific type of exposure, which hardly occurs in a normal environment, has been used in various studies to explore therapeutic use of magnetic fields Chen et al. The most interesting observation was that mice inoculated with Lewis lung cancer LLC cells and exposed to RMF for 35 days showed decreased tumour growth and increased levels of miRa in tumour tissue as compared with sham-exposed groups.

It should be interesting in the future to evaluate, using the same experimental conditions, the effects of the exposure on other cancer cells. On the other side, some evidence has shown that ELF-MF exposure can modulate endogenous neurogenesis, suggesting that it could be taken in consideration to treat neurological disorders Piacentini et al.

Four studies are reported below, whose research question was to explore if ELF-MF exposure could cause epigenetic alterations inducing effects on brain cells. Leone et al. They observed that ELF-MF exposure caused an enhancement of neuronal differentiation of NSCs and found that changes in histone acetylation were involved: in particular, ELF-MF-exposed samples showed an increased histone H3 acetylation at lysine 9 H3K9 on the regulatory sequence of several pro-neuronal genes.

Therefore, epigenetic modifications, particularly chromatin modifications at specific neuronal gene regulatory sequences, may be involved in the observed enhancement of hippocampal neurogenesis. Consales et al. In a more recent paper Consales et al. ELF-MF-exposed samples showed a significantly increase of methylation levels. Therefore, the authors concluded that the reduction of the expression of both miRb and miRc was caused by a decreased transcription of the common pri-miR due to the hypermethylation of the promoter.

In the experiments performed by Consales et al. Coherently, Snca transcript and protein levels were reduced in ELF-MF-exposed cells with the addition of an miRb mimic and increased in sham cells with the addition of anti-miRb. The same research group in a recent study Benassi et al. No significant difference was found between ELF-MF-exposed and exposed samples for all the experimental conditions tested. The authors concluded that the exposure to 50 Hz MF does not affect global DNA methylation in proliferating and dopaminergic differentiated SH-SY5Y cells, either under basal culture conditions or under neurotoxic stress.

In vivo study was carried out by Erdal et al. The animals used were male and female, young and mature, since previous studies reported that miR expression levels could change with age and sex Morgan and Bale Results indicated that all the six miRs were differentially expressed in response to ELF-MF depending on cell type brain or blood , age and sex Table 2.

The young female rats exposed to ELF-MF showed a significant decrease of the most part of the miRs analysed, whereas no statistically significant difference was observed in the mature females. Young and mature male rats showed some significant changes of miR levels both in the blood and in the brain tissue. Results of this study confirm that effects depend strongly on the cell type. The authors concluded that results provide evidence that long-time MF exposure in young rat, mainly female, can influence the expression levels of miRs in blood and brain and may be a risk factor for some neurological disease.

However, it is important to underline that miR regulation can be different between humans and rats. The four papers reported below Pasi et al. PEMFs are considered potentially useful for therapeutic purposes and have been also used in clinical applications because of their efficacy Arendash et al. Giorgi et al. However, most of the alterations were transient, indicating that cells can restore homeostatic DNA methylation patterns. The other three studies aimed at verifying if PEMF exposure could modulate the expression of miRs known to be involved in brain cancer Pasi et al.

Pasi et al. All these miRs have been reported to be upregulated in several human cancer types. T98G glioblastoma cells, which are resistant to chemo- and radio-therapy, were exposed to PEMF 75 Hz, 2 mT for 1 h and then subjected or not to treatment with temozolomide TMZ , a chemotherapy drug used to treat some brain tumours.

Changes of the expression levels were observed Table 2 : the most relevant result was that the expression of miRs was drastically reduced when the cells were treated with TMZ immediately after PEMF exposure. Capelli et al. A progressive reduction of the two miRs with the increasing time of exposure was observed, even if the differences between untreated and treated cells were not statistically significant.

Further research is needed, increasing the number of patients, to evaluate the significance of the data. Yao et al. Exposed samples exhibited accelerated OPC differentiation and higher relative expression of miRp than the control ones, indicating that PEMF exposure promoted the differentiation of OPCs via miRp upregulation. Thus, it was suggested that PEMF stimulation might have a potentially positive impact on the functional recovery process following severe traumatic demyelinating disorder.

Baek et al. Mll2 is a member of the trithorax trxG group, responsible for histone modifications during development. Mll2 overexpression led to a significant induction in H3K4me3 levels, which increased accessibility of several pluripotency-associated loci. Therefore, Mll2 could be a key mediator of the effects of electromagnetic fields during reprogramming. Interestingly, the same experiment was repeated by using a magnetic field—free system and it was found that generation of iPSC colonies was delayed through the suppression of epigenetic reprogramming.

This finding indicates that the environmental electromagnetic field energy is essential for favourable epigenetic remodelling during the acquisition of pluripotency. Later, the same research group Baek et al. It is widely accepted that PEMF exposure can promote osteogenesis, stimulating the osteoblast differentiation of human bone mesenchymal stem cells hBMSCs.

Indeed, this exposure has been successfully applied to improve bone regeneration in skeletal diseases and fractures Ongaro et al. In order to investigate the molecular mechanisms behind this phenomenon, De Mattei et al. At the end of the experiment, it was found that PEMFs regulated three miRs miRa, miRb, miRb that are involved in different phases of osteogenic differentiation and bone repair.

We found only 15 experimental studies that evaluate the effects of ELF-MF exposure on epigenetic marks. These studies are very heterogeneous in duration from 1 h to 60 days , mode of the exposure continuous or intermittent and physical characteristics of ELF-MF. Indeed, the magnetic field direction changing continuously in RMF with respect to sinusoidal and pulsed fields , its rise rapid in PEMF and smooth in sinusoidal alternating fields , the frequency itself and the intensity values are all parameters that might lead to different effects IARC Moreover, it is worth noting that some experimental conditions simulate the exposure which we are subjected to in our daily lives, whereas other types PEMF, RMF hardly occur in a normal environment but are investigated for therapeutic purposes.

The central role of the earth magnetic field in epigenetic reprogramming, found by Baek et al. The molecular mechanisms through which the various types of electromagnetic fields interact with organic molecules are not yet clear. One hypothesis is that the field induces changes in the energy levels of certain molecules through the radical-pair mechanism IARC ; Barnes and Greenebaum ; Sherrard et al.

This may affect concentration of free radicals, such as reactive oxygen species ROS. ROS can modulate cell signalling Finkel, , leading to biologically significant changes, including epigenetic ones Afanas'ev, ELF-MFs might interact with membrane targets, such as transmembrane ion channels, including those involved in calcium metabolism regulation Golbach et al.

Calcium signalling plays a role in gene expression and is also important in epigenetic regulation Puri However, for the time being, the chain of molecular events leading to epigenetic dysregulation is still unknown. Although data collected in the present review are still too few and varied to draw any conclusion, they are worth a closer examination. Most of the studies 13 out of 15 observed that ELF-MF exposure can induce an alteration of epigenetic marks.

When different researcher groups assessed the same marks i. Of great interest are the results reported by four papers, dealing with the effects of ELF-MF during cell differentiation Leone et al. They found that the exposure respectively promoted cell differentiation and iPSC generation. It was already known that electromagnetic fields can contribute to reprogramming of human skin fibroblasts Ventura et al. Indeed, differentiating and dedifferentiating cells are subjected to global changes in the epigenetic landscape; for this reason, they are highly sensitive to alterations induced by environmental agents including ELF-MF as compared to somatic differentiated cells, which are generally more epigenetically stable.

Some effects have been observed also in differentiated cells, but it is unclear whether these effects are transient or not and which are the potential long-term consequences for cell biological functionality. For the most part, data summarized here were obtained using in vitro systems consisting of monolayer cultures of cell lines, which are neoplastic cells. These models show some limitations: cancer cells exhibit numerous anomalies; in addition, conventional monolayer cultures lack the complexity of in vivo conditions.

There are a few promising studies, regarding the biological effects of ELF-MF exposure, that promote the use of 3D cell systems, thus providing more physiological conditions as compared to the conventional 2D cell cultures Hilz et al. Future research directions should be oriented to the use of nonneoplastic cells in 3D cell cultures.

Overall, current results constitute a good basis for future investigations and suggest that ELF-MF exposure could induce epigenetic alterations with major effects on cells undergoing differentiation and dedifferentiation processes. Further research is needed to understand the underlying molecular mechanisms. The acquisition of more knowledge on this topic could provide a basis both to develop therapeutic strategies and to prevent health hazards.

Epigenomics — PubMed Google Scholar. A systematic review. Curr Environ Health Rep —

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Zone inexploitable verticale 1. Consegna Prezzo. Spedizione Gratuita. Compila il form, aggiungi le caratteristice che preferisci e richiedi un preventivo personalizzato. Preventivo personalizzato ». Recensioni Approfondisci Prodotti correllati. Mostra altre recensioni. L'azienda offre stampe personalizzate su svariati tipi di supporto rigido come il classico cartone, il plexiglass, la carta, il PVC e naturalmente anche la stampa su Forex. Pannelli Forex: che cosa sono? Essendo il Forex una schiuma plastica rigida, risulta facilmente stampabile la struttura molecolare propria del PVC espanso infatti, ne rende la superficie bianca, liscia e omogenea.

Inoltre, sono leggeri da trasportare e da utilizzare per gli allestimenti e facili da lavorare. Inoltre, PressUP vi consente di plastificare a freddo il PVC con effetto lucido o opaco , in base a come volete la resa finale della stampa.

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