29 April 2009

Swine flu

Some notes on Swine Flu prepared mid-day 28/4/09

The Mexican outbreak of 18 March is of a H1N1 strain of influenza A virus. As was the Spanish flu of 1918, where lethality was high (50 x 10^6 dead: 500 x 10^6 infected worldwide).

Genome -- is 8 pieces of negative strand RNA. They can re-associate in mixed infections with other strains or sub-strains.

Proteome -- The genome codes for 11 proteins. Prominent coat proteins (therefore targets for antibodies) are Haemagglutinin (HA), Neuraminidase (NA), and M2 ion-channel. (A haemagglutinin coagulates blood by binding to red blood cells.) HA is cut into two by a host protease (forming HA1 and HA2) contributing to the great variability. The identity of the amino acid at the cut site can affect virulence.

Infection -- Droplet infection of the nose, throat and lungs (or contagion followed by subsequent touching of nose or mouth). The virus binds to sialic acid residues of glycoproteins on epithelial cells by way of the HA protein. The ingested virus in the acidic endosome would be subjected to digestion so it has to escape. It is thought that the M2 ion-channel has a role in releasing the RNA from the coat, and possibly the endosome. It may simply allow the virus interior to become acidic like the endosomal lumen. The RNA replicates first to a positive strand and from that to more negative strands. The daughter virion assembles its coat proteins near the inside surface of the host cell and buds out through the cell membrane. Only some 10% of progeny contain the correct 8 pieces of RNA. The NA protein's sole function is to cut the progeny virus away from the now dying host cell.

Lethality -- arises because the virus activates a cytokine storm, a feed-back loop between cytokines and immune cells. There are many cytokines including tumor necrosis factor alpha, and interleukins; and of the interleukins some are inflammatory (e.g. 1 and 6) while others are anti-inflammatory (10 etc.). A storm in the lungs causes inflow of macrophages which destroy lung tissue and cause inflow of liquid; and respiratory distress. It is a striking feature of death by cytokine storm that it is those with the BEST immune response who die; healthy young 15 - 40 year-olds. (I wonder if aspirin might save lives! I shall certainly take aspirin with me if I go to Mexico [See J. Biol. Chem. 272, pp. 25693-9])

Chemotherapy -- The two main targets are M2 protein (blocked by amantadine, and its relatives, which cause drug resistance if overused), and Oseltamivir (= tamiflu, etc.) and other similar drugs which are neuraminidase inhibitors. These are not effective against the cytokine storm. 

Vaccines -- Though there are vaccines already prepared against H1N1 strain of influenza A, they are not effective against this sub-strain. Illustrating the VARIABILITY of the HA and NA antigens. With new methods, effective monoclonals can be made in some 6 weeks against the specific sub-strain involved, for use in passive antibody therapy.

Why lethal in Mexico but not elsewhere? -- I suppose that there is recombination at work; my speculation is that Europeans already have immunity to one of the parents of this new sub-strain.


--
Ian West
12 Longhirst Village,
MORPETH, NE61 3LT, UK
Tel: (0)1670 791880






03 April 2009

Florentine Humanism

Humanism in 14 © Florence

From the Latin Humanitas = human nature. Cicero spoke of Studia humanitatis ac litterae in exactly the sense in which the Renaissance took it up 1300 years later.[1]

Humanism was originally a specific system of education favoured in late 14th century Italy by the wealthy. (Those who had to earn a living, e.g. in commerce or craft, favoured Abbaco education in the vernacular comprising Reading, Writing, Mathematics, and the Bible.) Humanistic education (Humanae Litterae or Humane Letters) was based on the education of Roman times and was conducted in the Latin language. It comprised Grammar, Rhetoric, Poetry, History, and Moral Philosophy; supposedly humanizing and civilizing, but there was always the hint of a contrast with the 'divine'. The term survives in the same sense at Oxford where you can still study Litterae Humaniores.

Renaissance Humanism did not start in Florence, but in the much older Universities of Padua (1222) and Bologna (1088); Latin scholars there have been referred to as Pre-Humanists.

The Founding Humanists – Petrarch and Boccaccio

Petrarch (1304 – 1374) could be said [2] to have started the craze, and is credited both as "Father of Humanism" and "Father of the Renaissance". Petrarch, an ex-pat Florentine, studied Law at Bologna University, but gave that up in his early twenties saying "I couldn't face making a merchandise of my mind". He gained his living in small clerical jobs, but dedicated his life to writing. Petrarch wrote immortal poetry, both in content and form. (His invention of the Sonnet conquered the world and has not been superseded.) He was the first poet laureate since classical times (crowned 1341); revered throughout Italy, and indeed Europe. Petrarch was aiming at a purer more sophisticated language (he famously described the Latin of the Middle Ages as "barbarous"), but also an elevation of the status of the human individual as a work of God. He personally searched out and discovered lost Latin texts (e.g. Cicero's letters). Petrarch wrote mostly in Latin modelled on Cicero and Seneca; but he knew no Greek. His humanism was perhaps chiefly aesthetic.

Boccaccio (1313 -- 1375), the illegitimate son of a minor Florentine official, trained in banking and the law, neither of which suited him, but the latter taking him to university opened him to the culture of humanism (c.f. Petrarch). He wrote verse but also prose, writing in earnest when his father died of the plague in 1349, but also worked for, and travelled widely for, the city. He was selected by the city to greet and entertain the illustrious Petrarch when that man visited Florence in 1350. Glimpsing the grandeur of Homer, he pushed for the introduction of the study of Greek, but there were still no adequate teachers in Italy. He tried unsuccessfully to get Petrarch to come to teach at Florence University [3].

Two of the prominent early Florentine humanists were both Chancellors (i.e. chief bureaucrat of the city, recording details of city transactions); namely Salutati (1331 – 1406, and Bruni (1369 – 1444). They no doubt enjoyed in Florence the humanist education and the access which that gave them to Latin literature. Both men wrote extensively themselves; Salutati, a confused jumble of views both for and against monarchy. Bruni on the other hand is credited as the first modern historian.[4] The old-style history sought to trace the implementation of God's plan. Bruni, by contrast, studied the history of Rome and Florence seeking causes, and in order to improve. A contemporary (Piero Beccanugi) in 1413 used the phrase "Seeking to administer public affairs intelligently....", a remarkable concept. We also have the remarkable spectacle of politicians quoting Seneca to justify their actions.

War with Milan and Genoa – Civic Humanism.

In 1402 Florence found itself at war with Milan, and ten years later with Genoa. These unsatisfactory conflicts had a dramatic effect on the intellectual life of the city. Remember that Florence was then a Guelph, and very bourgeois city; the dominant group at the time included these liberally educated, humanist, and republican citizens  -- epitomized by Bruni. The political stresses of the times strongly politicised the intellectual middle classes who asked themselves some hard questions about the effectiveness of their institutions and how they could be improved. Anyone who could think became a "Civic Humanist". [5]

Renaissance not a popular movement – role of Medici

Bertrand Russell points out [6] that the renaissance was not a popular movement; it involved a relatively small number of scholars and artists supported by wealthy patrons (notably the Medici and the Humanist Popes like Nicholas V and Sixtus IV). Cosimo de Medici (1389 – 1464) was (of course) subjected to the Humanistic education of the period, and was greatly taken with it. While a youngster he mixed with a racy bunch of enthusiasts, including Niccoli (1364 – 1437) the handsome, argumentative, aesthetic son of a rich wool merchant who spent his entire fortune (and part of Cosimo's) acquiring manuscripts.[7] Niccoli, 25 years Cosimo's senior, suggested a trip to the Holy Land in search of Greek manuscripts, but Giovanni de Medici would not allow it and sent the young Cosimo back to the bank. Niccoli had no judgement, but lovely handwriting, inventing what we now know as Italic cursive script. (Remember that printing was not introduced from Germany till 1471; all books were copied by hand). In 1439, when Cosimo was 50, he became captivated with the idea of Greek Philosophy; and of studying it vicariously through others. He brought into his household Marsilio Ficino (1433 -- 1499), the young son of his physician, who became adept at Greek and translated into Latin all the works of Plato so that Cosimo could read them. In 1462, 2 years before his death Cosimo, sufficiently impressed with the 29 year old Ficino, gave him a villa at Careggi to found the Florentine Academy in imitation of Plato's Academy in Athens.  The academy was supported in his turn by Lorenzo de Medici. Ficino was enthusiastic and industrious, but uncritical as a philosopher (See below under Plato).[8]

Greek versus Latin

Initially Humanism, realizing that medieval Latin was degraded, enthusiastically studied the great Roman masters of classical Latin, which were relatively available and easy to understand. By 1400 it was clear to enthusiastic Humanists that there was an entire culture lying behind Latin, namely Greek! There were the great philosophers, and the great dramatists, neither of which the Romans could match. So there arose a great hunger for things Greek; but there were no teachers. (It is worth noting that Greek was known in England, Scotland and Ireland throughout the Dark Ages.) Two events contributed to bring Greek to the Florentine Greekomaniacs. The ecumenical council of Ferrara (1438 – 1449), intended to heal the rift between Eastern and Western Christianity, was, at the urging of Cosimo de Medici, in January 1439 invited to transfer to a somewhat xenophobic Florence. There, for a period of years, lived and paraded through the streets these astonishing Priests with their funny hats, their monkeys and their servants. Some stayed in Italy after the council ended (Pletho and Bessarion). Then there followed, soon after, the fall of Constantinople to the Turks (1453) and a great efflux of men and manuscripts. To his distress, Cosimo never mastered Greek, and had to read the Greek masters in Latin translation.[8]

Humanism versus Scholasticism (Plato versus Aristotle)

Aristotle was well know to the Middle Ages, entering Europe via the Muslim faylasufs, particularly Avicenna (Tehran) and Averroes (Cordova) who wrote extensive commentaries on (in particular) Aristotle. Thomas Aquinas, brought up in the Muslim-influenced Sicily, attempted an assimilation of Aristotle into Christianity; this was the great age of Scholasticism; commentaries on commentaries, but no texts. The slogan of the Humanists was "Ad fontes". Once the Greek masters were available to the renaissance scholars they could see that Aristotle was not the only philosopher; a vigorous debate was opened. Bertrand Russell, who was very dismissive of renaissance philosophy, wryly remarked [6] that this debate encouraged independent thought, at least to the extent of choosing between Plato and Aristotle. The contrast between these two is striking. Aristotle was a naturalist, Plato a mathematician; Aristotle sought knowledge, Plato Wisdom. Aristotle is plodding, comprehensive and dull; Plato mystical, seductive, and poetic. Plato had a more 'Christian', i.e. complex, concept of God, and entertained a notion of the 'immortality of the rational soul' [9].  Both Cosimo and Lorenzo were addicted to Plato, as was their protégé Ficino. The latter found in Plato a unity of philosophy and poetry which completely overawed him: "I consider Plato's style is more like that of a divine oracle than any human eloquence".[10] I.e. Ficino went over the top; he was even more fascinated by Greek Astrology than by Greek Philosophy.[6,10]

Nevertheless, extant texts from the period are 200:10 in favour of Aristotle over Plato.

Relationship of Humanism to Christianity

Humanism was originally the harmless, indeed exciting, discovery of ancient civilizations that emphasised beauty, and human and individual worth; several of the Popes were keen Humanists, collecting, commissioning and building. But Humanism went on to discover that the ancients entertained many ideas besides those taught by the Catholic Church. From ornament to alternative, from alternative to threat. The debauchery, avarice and criminality of the Papacy were disgusting, not because they were more extreme than elsewhere at the time, but because they should have been less extreme. Many humanists reluctantly supported the Church because that was where their patronage came from; but others were openly scornful.  In any case, most saw no middle way between orthodoxy and Free Thought. The doctrine of Purgatory was immensely remunerative for the Church. The Eastern Church regarded it as heresy but was too weak to insist. It took Luther to abolish purgatory, and with it the wealth of the Western Church.

 The end of the Renaissance

The renaissance ended perhaps with the sack of Rome by Emperor Charles V in 1527 and his annexation of Milan in 1535; the bickering between petty states had finally led to foreign domination. Or maybe the renaissance ended with the Council of Trent (1545 – 64), for the corrupt Church was finally goaded into reforming itself, which it did with the recognition of the Jesuits (1540) the establishment of the inquisition (1542) and the Index of banned books (1559). Perhaps the new learning simply matured; the Ancient world was no longer regarded as the fountain of truth and thinkers turned elsewhere (e.g. Copernicus (1473 – 1543), Galileo (1564 – 1642)). However, the end of the renaissance was arguably heralded earlier, with the discovery of America (1492) and the sea route to India (1497 - 9) and China, for the Mediterranean ceased to be the centre of the world, and became a backwater. Venice, Florence, and Genoa were no longer on the great trade route connecting West and East. The world's wealth poured instead into Iberia and the Low Countries, (and eventually Britain).

References

1. Nauert, CG (2006) "Humanism and the Culture of Renaissance Europe"
2. http://en.wikipedia.org/wiki/Petrarch
3.  http://en.wikipedia.org/wiki/Giovanni_Boccaccio
4.  http://en.wikipedia.org/wiki/Leonardo_Bruni
5.  http://plato.stanford.edu/entries/humanism-civic/
6.  Russell B (1946) "A History of Western Philosophy"
7.  http://en.wikipedia.org/wiki/Niccol˜_de'_Niccoli
8.  Hibbert, C (1974) "The rise and fall of the house of Medici"
9.  http://easyweb.easynet.co.uk/~orpheus/ficino.htm
10. http://cura.free.fr/decem/10voss.html

Ian West, 30th March 2009


02 April 2009

Bacon and the Novum Organum

Bacon and the Novum Organum

I was interested in Melvyn Bragg's program "In our Time" devoted to Francis Bacon (as I am to all his programs in that series), and I learnt much even though I have regarded myself as an ardent Baconian for over forty years. But I think something slipped through his fingers – namely the inductive method. It is not that the members of the discussion panel did not know the material, for Patricia Fara clearly had it at her finger tips and could have given an excellent exposition. Perhaps the focus of the program was elsewhere. Perhaps none of the panel were practising scientists.

I read the Novum Organum in the summer of 1965 at the end of my first year as a D.Phil student at Oxford. I had already some knowledge of the process of practical science in the twentieth century, of designing experiments, and collecting data. I had also been attending Rom Harré's lectures on the "Philosophy of Science" and AJ Ayer's on "Induction". In that context Bacon's modest little book came as a beacon of light in a dark seascape. "Induction is logically impossible", said Hume (and Ayer); "you cannot win a general truth from particular observations". "Induction is not necessary in Science", said Popper; "you merely make observations, and falsify hypotheses." But where, I wanted to know, do you get your hypotheses in the first place? No one could help me with that question. No one even attempted to help me. I decided that philosophy, while fun, was best relegated to after supper musings. So, in the summer of 1965, it was a big surprise to me to find that Bacon had answered the problem a hundred and fifty years before Hume had raised it. What chiefly fascinated me was that no one referred to Bacon; neither the philosophers nor the scientists. Of course, he was not wiped entirely from the pages of history; a sprinkling of people knew about Bacon 'catching his death' while trying to preserve a dead chicken with snow. Another smaller sprinkling knew of his impeachment for embezzlement. But my scientist colleagues did not know of his Novum Organum.

The New Organon is more than a pyramid, as explained by one of Melvyn Bragg's panellists; and though it is indeed a matter of drawing up lists, as explained by Patricia Fara, it is more than that also. Its power can be seen in its results; Bacon concluded that heat is motion some 200 years ahead of the field! But Ssh! I feel like a traveller about to let slip to the general public the whereabouts of a perfect picnic spot. There is no need for everyone to know everything, surely!

Ian West, Morpeth, 2 April 2009