York Minster

Christians often debate whether natural disasters are signs of the punishment of God. After all, insurance companies often refer to them as "Acts of God". Recently some Christains have suggested that Hurricane Katrina was a punishment on New Orleans, a self promoted City of Sin. Of course that begs the question of why Las Vegas is still standing, but we might examine whether there are Biblical grounds for suspecting this.

There is a history here. The Genesis Flood was apparently punishment on the whole earth for their sinful ways and the destruction of Sodom and Gemorrah was as a result of the Angels failing to find even 10 righteous people.

On the other hand the evils that beset Job were the consequence of God giving permission to Satan to test him to demonstrate that he wasn't what we would nowadays call a rice Christian. In Luke Ch 4 Jesus himself warns us not to assume that those on whom disaster falls are greater sinners than the rest of us - those whose blood Pilate had mixed with their sacrifices (v 2) and those on whom the Tower in Siloam fell (v 4).

However, early in the morning of the 19th July 1984 York Minster was partially destroyed by fire shortly after the installation there of the heretical David Jenkins as Bishop of Durham. It had apparently been struck by a lightning bolt out of a cloudless sky. Some Christians at the time saw this as an Act of God. Jenkins had denied the bodily resurrection of Jesus, saying he wasn't interested in a "conjuring trick with bones". They said that it was just what God would do when mankind had tried His patience just too much; nobody was even injured. The magnificent Rose Window was destroyed - but that could be seen as an example of idolatry. There was more concern over the destruction of a work nof art than about an insult to God, or about an intellectual damaging the simple faith of thousands of ordinary Christains.

This suggestion met with short shrift from the hierarchy of the church. A vengeful God like that was not what Christianity was about.

In response I wrote this poem - not because I necessarily thought that God would rain down lightning vengeful bolts, but because I objected to the complacency that assumed that he would for ever restrain Himself.

York Minster

Would you really
Rain fire down merely
Because of doubting?
Really flame those windows out
Fusing fine and thrilling lines
Of laid up treasure?
Derive pleasure from unmaking?
Want us quaking,
Knees shaking,
Slaking the pride of God the vandal;
Who wreaks havoc and upheaval
On one small, self-seeking scandal?

No, God is love and meekness, kindness:
Shows complete, benevolent blindness
To our foibles.
Long suffering, He forgives, forebears,
Does not notice when we err.
Forty-winks at deviation,
Falling short or reprobation.
Wouldn’t make a fuss
About us. Don’t worry,
Gomorrah will be here tomorrow.
Sodom is safe.

John Updike on Easter

I could not resist this Easter poem by John Updike.

SEVEN STANZAS AT EASTER

Make no mistake: if he rose at all
It was as His body;
If the cell’s dissolution did not reverse, the molecule reknit,
The amino acids rekindle,
The Church will fall.

It was not as the flowers,
Each soft spring recurrent;
It was not as His Spirit in the mouths and fuddled eyes of the
Eleven apostles;
It was as His flesh; ours.

The same hinged thumbs and toes
The same valved heart
That—pierced—died, withered, paused, and then regathered
Out of enduring Might
New strength to enclose.

Let us not mock God with metaphor,
Analogy, sidestepping, transcendence,
Making of the event a parable, a sign painted in the faded
Credulity of earlier ages:
Let us walk through the door.

The stone is rolled back, not papier-mache,
Not a stone in a story,
But the vast rock of materiality that in the slow grinding of
Time will eclipse for each of us
The wide light of day.

And if we have an angel at the tomb,
Make it a real angel,
Weighty with Max Planck’s quanta, vivid with hair, opaque in
The dawn light, robed in real linen
Spun on a definite loom.

Let us not seek to make it less monstrous,
For our own convenience, our own sense of beauty,
Lest, awakened in one unthinkable hour, we are embarrassed
By the miracle,
And crushed by remonstrance.

Climate change 2

One of my correspondents takes me to task for swallowing the Climate Change Deniers Handbook. On climate change I am not an atheist, but an agnostic. I am not an expert on this, but I know enough about experts to take what they say with a pinch of salt. For true believers you might try http://illconsidered.blogspot.com/2006/02/how-to-talk-to-global-warming-sceptic.html as an alternative to the website I posted last time.

What I am sure about is that if there is a problem to be dealt with it will not be solved by self-denial. China and India and eventually Africa are going to want the same sorts of luxuries and mobility that we enjoy in the West. Better technology has to be the answer.

With that in mind I was interested to read the following article in the Washington Post yesterday. http://www.washingtonpost.com/wp-dyn/content/article/2006/04/14/AR2006041401209.html

Patrick Moore, the co-founder of Greenpeace has joined James Lovelock, the inventor of Gaia, in calling for an expansion of nuclear power. He makes the cogent point that deaths from nuclear power are far fewer than from coal mining or drilling for oil. Even what might happen if a highjacked aeroplane flew into a nuclear power station has been greatly exaggerated.

I have been a long-term supporter of nuclear power - even to the extent of losing money by investing in nuclear power stations on ideological, rather than pecuniary, grounds. Of all forms of power generation I have long thought coal was the worst. I have seen chest X-rays from miners and been down a coal mine. One of my great heroes is Lord Shaftesbury, who got the women and children out of the British coal mines. I predict that one day Lord Hesseltine will be thought of in the same way. He was the politician who effectively got the men out of the Brittish coal mines. Just after the second world war there were close to a milion men who worked down the mines. Now that number is just a few thousand.

Working down a coal mine is a dirty and disgusting job that inflicts health problems on the miners but until recently gave them an unhealthy grasp on economic power. In the UK Mrs Thatcher was able to break that economic stranglehold by facinmg down Arthur Skargill. Those same economics have now handed that same power to a few unstable states in the Middle East. I have little doubt that were it not for the oil the West would take as much interest in who rules in Iraq as they do in who rules in Darfur. On the other hand I do not buy in to the conspiracy theories that have Bush and Cheyney personally enriching themselves; rather it is a case of the West being vulnerable to cutting off of oil supplies, and seeking to ensure that their supplies are secure.

When people ask why if regime change was the real reason for the invasion of Iraq, does not the Western Alliance march into Zimbabwe or North Korea, the answer is that those countries do not control our oil supply.

So you admit it is about oil?

Only in the sense that currently the world's economy depends on oil which thrusts it into an undeserved importance. The real solution is to divest ourselves of our dependence then we could allow Shias and Sunnis to squabble over the desert to their hearts' content.

Easter

In her despair Mary was comforted.

In his doubt Thomas was assured.

In his shame Peter was restored.

Christ is risen!

He is risen indeed!

Hallelujah!

You're nearer to God in a garden

Today was spent painting. My super-strong, guaranteed-ten-years, black paint was applied to the window frames. And not a moment to soon - the drizzle started shortly afterwards. This is the making of England's green and pleasant land. Warm April showers are marvellous for the garden where buds are on every bush and tree. Row upon row of grape hyacinths are standing like light blue soldiers in their green foliage. The heathers are brightly garbed in purple and white. In the greenhouse the geraniums have successfully over-wintered. The strelitzia is about to burst orange and the bougainvillea is showing signs of life. On the top branch of the cherry tree a lone robin is whistling.

I think we'll leave those anonymouses (or should it be anonymice) arguing among themselves and change the subject.

This is a story about the pointlessness of wealth. A very rich man was told by his doctor that he was going to die. This caused him dismay as he had often been told that he couldn't take it with him. He was a believer and because he had made a commitment to Christ at a Presbyterian church early in his life and he had been told, "Once saved; always saved," and therefore he was certain that he was going to heaven, but the thought of leaving all that he had worked for behind him was unimaginable.

That night he prayed vehemently to God, "I can't leave all this behind; please let me bring something with me."

As he was sleeping an angel appeared to him in a dream. "There are no pockets in a shroud, " he said, "You must leave it all behind."

Even more dismayed, the next night he prayed even more vehemently, "Lord, you have prospered me all my life, surely you don't want me to abandon all these blessings you have given me."

In his dream that night the angel came and this time said, "God has relented; you may bring one suitcase."

The next morning he rang his broker and told hime to liquidise everything and turn it into gold so that that night, as he went to sleep, he had beneath his bed a suitcase full of gold ingots.

In the night he died and he began dragging this heavy suitcase up to heaven. It was an arduous journey, but he finally arrived at the pearly gates. St Peter stopped him. "I'm afraid you can't come in here with a suitcase. You must enter heaven with empty hands."

"But God has given me a special dispensation. He said I could bring one suitcase."

St Peter sent an angel to ask God if this was true and when he returned the angel said, "God did give him this dispensation, but he says that you must check for contraband."

St Peter opens the case and stares at the gold with astonishment.

"Paving stones?" he says, "You've brought paving stones?"

Iraq - influences of the Thirty Years War

My last post uncovered how polarized is American public opinion. I suppose that such invective and vigorous argument is a symptom of a healthy democracy. However, I am reminded of one of my favorite books which is entitled "The Great Virtues". The author states that the first and fundamental virtue is politeness, for without politeness there can be no discussion. I would also remind readers of my plea not to post anonymous comments unless there is a real reason to do so. Since so many of my readers are patients, it is quite reasonable for them to keep their personal details confidential, but political opinions ought to be owned by their authors, and if not they assume the status of the anonymous letter written in green ink, which I have always, whether they praised or abused me, crumpled up and filed in the round filing cabinet beneath my desk.

My purpose in writing about Iraq was not to stir up a hornet's nest nor to apportion blame, but to explore the basis of what some have called a 21st Century conflict played by 20th Century rules. The following link leads to an important contibution to this debate made by the British Defence Secretary, John Reid.
http://www.mod.uk/DefenceInternet/DefenceNews/DefencePolicyAndBusiness/
ReidAddressesRusiOn20thcenturyRules21stcenturyConflict.htm

If we think that the current war is unpleasant a return to the time of the Thirty Year War in Europe is terrifying. This was one of the few wars in history that England managed to keep out of. It was within this period, 1618-1648, that we had our own civil war, which had similar origins - the conflict betwen Catholics and Protestants.

My knowledge of this period of European history it is very minimal, and mainly garnered from a fascinating book called "Q" written under the pseudonym of "Luther Blisset" by four Italian anarchists, Fredrico Guglielmi, Lucia Di Meo, Giovanni Cattabriga and Fabrizio Belletati. http://mostlyfiction.com/history/blissett.htm Luther Blisset was one of the first black footballers to have a successful career in England. He played for Watford, the football team owned by singer Elton John, but was transferred to AC Milan where he was certainly a character, though not an outstanding success. He finished his playing career here in Bournemouth, where under their successful manager, Harry Redknapp, his career had a late flowering. He owned a sports equipment shop just round the corner from my house. Harry's children were at school with my oldest boy.

The book is about the Peasants War (one hundred years earlier than the Thirty Years War) written from the point of view of the anabaptists (anarchists like the authors). However, the reasons behind the Thirty Years War were similar, revolving around the relationship between religion and statehood, and the conditions of the protagonists were similar. It is a good read to reveal the brutality of war in the 16th and 17th centuries.

The Thirty Years War was in part a religious war. Although in Germany the various Principalities had achieved self rule and established Lutherism for 75 years, and had reached a Truce with Rome at the Peace of Ausberg in 1555, the consequences of the Reformation were certainly not settled. The Protestants had split between Lutherans and Calvinists, and Calvinists were not included in the truce. Anabaptists were as much enemies of Luther as they were of Rome. The Jesuit counter-reformation had taken hold, so that there was a powder keg in Germany waiting for a match to set it alight.

The Spanish Netherlands had become Protestant and thrown off the Spanish yoke and were allied with France. Although France was Catholic, its long standing rivalry with Spain had meant that my enemy's enemy is my friend. Spain in seeking to re-establish its authority over the Netherlands could not sail there (since the defeat of the Armada in 1588, England held the Channel), but must take an overland route via Northern Italy, the Alps and Southern Germany. The Holy Roman Empire and Spain were both ruled by Hapsburgs. France felt at risk from a Hapsburg encirclement. Only the assasination of Henry IV in 1610 averted war then.

Denmark and Sweden were also at odds. Scandinavia had once all been ruled by the King of Denmark, but Sweden had broken away. In an attempt to restore its authority Denmark unsuccessfully attacked Sweden in 1611. There was a dynastic struggle in Sweden as the King of Poland had a better claim to the throne than Gustavus Adolphus. But Sweden was Protestant and Poland Catholic - the Spain of the North. To put pressure on Poland, Sweden allied herself with the Russian Tsar, Boris Gudunov. Boris was overthrown and Sweden then allied herself with both Holland and the Evangelical Union in Germany.

Bohemia (the modern Czech Republic) provided the spark for war. The region was a mixture of Calvinists, Catholics, Lutherans and Anabaptists who lived in harmony. In 1617 Archduke Ferdinand of Styria became Holy Roman Emperor and determined to reimpose Catholicism on Bohemia. In protest two Catholic deputies (Martiniz and Slavata) were defenestrated in Prague. This was a classical Czech habit of chucking people out of windows. They were not hurt; they landed in a dung heap (unlike Jan Masaryk who was murdered this way by the Communists in 1948). This was an insult to Ferdinand (who was to become Holy Roman Emperor) and following a dispute over the succession to the Kingdom of Bohemia he defeated the army of Frederick, Elector of Palantine at the Battle of White Mountain, and expelled the Protestants from Bohemia. This laid down the gauntlet and the Protestant countries picked it up. War raged for 30 years.

After early victories by the Catholic generals Tilly and Wallenstein, Gustavus Adolphus entered the conflict and took control of Germany. A restored Wallenstein hindered Gustavus and though defeated at Lutzen so that he had to retreat to Bohemia, Wallenstein inflicted important damage on the Protestants; Gustavus was killed. Swedish power was now at its zenith. Wallenstein exceeded his authority and began making peace treaties. He was murdered by his own officers. In 1634 a major battle at Nordlingen saw the Protestant army defeated and the Peace of Prague ensued. This provoked France into re-entering the war and allied herself with Sweden, the low countries and some Northern Italian states. Cardinal Richelieu (yes we're in Three Musketeers' territory) had several setbacks at first, but managed to repel the Spanish invsion. Spain suffered naval defeats by the Dutch and the French and even at home there were embarrassed by a Catalan rebellion. Defeats for the Empire at Nordilgen (again) by the French and at Jankau by the Swedes meant that it could no longer carry on, but neither France nor Sweden could push home their advantage. By 1645 military exhaustion had set in throughout Europe. Millions had been killed, plague had ravaged populations, agriculture had failed and nations were bankrupt. It was estimated that urban areas in Europe had suffered a 33% population loss and rural areas a 40% loss.

The Peace of Westphalia in 1648 ended the Thirty Years War. It is considered by historians to mark the beginning of the modern era. As a result of the Peace Accord the Netherlands finally gained independance from Spain, ending 80 years of conflict. Sweden gained some teritory in Northern Germany. The power of the Holy Roman Emperor was finally broken, but Germany remained a group of 360 independent and seperate principalities. Calvinists were given legal recognition. France was the overall victor; it acquired Alsace and Lorraine and a vote in the German Reichstag. Switzerland was recognised as a fully independent nation.

The most important consequence was that it ended for all time the idea that the Holy Roman Empire having secular dominion over the entire Christian world. The nation-state would be the highest level of government subservient to no other. No state had any right to determine how another state undertook its business.

In Mein Kampf Hitler states that the Treaty of Westphalia cemented Germany's internal divisions for over 200 years and prevented Germany acquiring an Empire like Britain's or France's. Communism predicted the demise of the Westphalian system seeing it replaced by an International Workers' Union. In 2004 in the aftermath of the Madrid attacks, Lewis 'Atiyyatullah, an al-Qaeda spokesman, predicted that the Westphalian system would collapse and be replaced by a system under the leadership of a mighty Islamic state. In 2000 Joshka Fischer, the German Foreign Minister, predicted that the Westphalian system of nation states would be replaced by a supranational European Institution.

What can we learn from the Thirty Years War? First, that to assume that a decisive battle imposes your will on another nation state by force is to deceive yourself. War must either be prosecuted to ultimate and complete victory or else it sows the seeds for the next conflict. Second, in the end you have to negotiate a settlement that satisfies all parties. Third, you cannot change men's minds on religion by force. Fourth, people of different religions can live in harmony with one another when they accept conclusion 3.

We need to reconsider whether the sovereign nation-state is subservient to no other. Is it right for a national leader to attack a section of his own people because of the color of thei skin, their religion, their politics or what they write or say? Who is to defend their human rights?

Iraq: where did it all go wrong? Part 1

Civil war in Iraq? Bush's popularity at an all time low? Where did it all go wrong?

It has been a long term United Nations maxim that the internal affairs of a country are its own business and not to be interfered with by other countries. The fact that both the USSR and China had nuclear weapons probably had something to do with the fact that neither the US nor the UK sent an army to those countries to correct their despised forms of government.

It was not always so. Palmerston's means of conducting foreign policy was to send a gunboat, and until 1945 most nations saw war as a more active branch of diplomacy. The formation of the United Nations established a natural stalemate, with the Soviet Union unwilling to agree to any American-led war. Modern air travel would have prevented the Korean War since it was only approved by the Security Council because the Soviet representative arrived too late to say no.

War thereafter was largely a by-proxy practice. When Britain and France were made to back down over Suez by America's economic threats there seemed little chance of any nation starting a war of acquisition, or even to retain what they had bought and paid for.

The second half of the 20th century was marked by a series of small wars of independence as new nations threw off their erstwhile colonial powers. It was strange to see America, a nation formed by a revolution against the colonial power, again and again taking the side of the bosses against the little man. This had the effect of throwing the revolutionaries into the hands of the Soviets, who imposed their brutal form of totalitarianism on them. Was it necessary for Cuba to become hardline Marxist? Heaven knows the Batista regime was evil enough to need overthrowing. The unsavory picture of Kennedy, the Massachusetts liberal, in bed with casino-owning Mafiosi is unedifying enough, but the sort of foul governments supported by the US in South America during this period in the name of stopping communism is shameful.

The culmination came in Viet Nam. What started as a war of independence in French Indo-China became a surrogate hot-spot in the cold war. In retrospect the wisdom of the British in leaving India and Burma in 1947 is apparent. The capitalist societies in Viet Nam and even China demonstrate that Soviet style uniformity and oppression holds no attraction for ordinary people.

In the fifteen years after World War II communism became a colossal boogie-man to America. Several strands contributed to this. The stealing of the nuclear secrets by Klaus Fuchs, the outcome of the Potsdam conference, allowing Stalin to run Eastern Europe as vassal states, the McCarthy hearings, Churchill's iron-curtain speech, the Korean War, and the launching of the first Sputnik in 1957 all contributed. I suspect that America's isolation was a major factor. Such a vast country, so self-sufficient, so ignorant of the outside world; Americans were unable to assimilate communism into their political spectrum, in the way that France or Italy did, and unable to ridicule it in gentle way that Britain did.

So, the Domino Theory demanded that Viet Nam was defended and became America's nemesis. Defeat in Viet Nam did not happen on the battlefield, but on the University Campus. Young Americans became disgusted by what the military was doing. This defeat lodged in the American psyche and emasculated the country for a generation. It was reinforced by Carter's abortive attempt to rescue the Iranian hostages and by the Black Hawk Down defeat in Somalia.

Meanwhile, Britain had discovered a new virility. After a failed experiment with socialism which left the dead unburied and rats in the street nibbling at uncollected garbage, Mrs. Thatcher put backbone back in the nation by defeating the Argentineans in the Falklands.

This was a clean war. It was in response to a call for help from the indigenous people who were of British extraction and willing colonials. It was fought against a regime widely recognized as evil, a dictatorship kept in power by brutal police action against its own people who had modern weapons sufficient to destroy several British warships. It was won by the heroism of tough soldiers who marched across rough terrain in filthy weather to defeat the occupiers in hand to hand combat when the helicopters that were meant to allow them to fight like Americans were sunk with the Atlantic Conveyer, a container ship that the Argentinean pilots mistook for an aircraft carrier. Not only were the Falklands secured, but the Argentinean tyranny was overthrown at home.

In some ways the first Iraq war was similar. The invading power had long claimed the invaded land as its own. It was ruled by a sinister dictatorship. In the circumstances it was not difficult to put together a huge coalition that even included Syria. This war was different from the Falklands, though. It was won not by individual heroism but by overwhelming fire power and military superiority. It was won by the Americans; her allies were make-weights, there to give the semblance of world unity. The invaded country was not populated by poor farmers but by oil-rich Arabs and contract workers who had no say in how the country was run.

Colin Powell stopped on the road to Baghdad when it got too much like shooting fish in a barrel. Saddam survived. To have removed him would have had the Arabs deserting the coalition. In retrospect I think this was a mistake and one that would not have happened if Mrs. Thatcher had not been deposed during the build up to the war. She was adept at pulling the strings.

Just as Thatcher had restored Britain's self confidence, so Reagan restored America's. The defeat of the Soviets in the cold war was done by bravado. It was a poker game in which America kept upping the ante until the Soviets folded.

In the nineties small nations started behaving badly. Perhaps the Russians had been restraining their client states during the cold war. A free hand was given for ethnic cleansing. In Yugoslavia, Indonesia and Africa atrocities abounded. The West was shamed into intervening. In East Timor the Australians went in to protect the Christians from the Moslems, in Kosovo Clinton and the EU went in to protect the Moslems from the Christians, but nobody had protected the Catholic Tutsis from the Catholic Hutus and nobody had protected the Bosnian Moslems from the Serbian Orthodox and no-one had intervened between the Catholic Croatians and the Orthodox Serbs, and still nobody intervenes between the Shona and the Matebele in Zimbabwe or between the Moslems and the Christians in Sudan.

Who should police the world? From Pax Romana to Pax Britannica it has been the role of the strongest nation to act the magistrate. America had been reluctant to do so. After 9/11 things changed.

Attacking Afghanistan had near universal support. Bin Laden had sought sanctuary there and he was behind the Twin Towers disaster. The Taliban would not give him up and in any case they were a repressive, intolerant regime that cut off the hands of thieves and destroyed ancient statues of the Buddha. The success in Afghanistan must have encouraged Bush to go on down his list. Saddam was unfinished business. In those days everybody believed in WMD even if they were only believed to be a battlefield threat.

Regime change was the real motive behind the Iraq war. Saddam was indeed an evil tyrant. The destruction of the Marsh Arabs after Gulf War I was something that America felt guilty about. Encouraged to rebel they had been abandoned by the coalition. Saddam's retribution was harsh. The UN had instituted sanctions, but they were being evaded. Saddam was building palaces while children starved and the UN, not Saddam, was getting the blame. There was a movement to lift the sanctions.

Saddam was in a cleft stick. He had no WMD, but his hold on power depended on the pretence that he did. He stalled the weapons inspectors so as to keep up the pretence as long as possible. The UN passed resolution 1441 threatening worse than sanctions if the weapons inspectors could not do their job. But if he let them do their job and they found nothing then for him it would be worse than sanctions. Besides he did not believe that the Security Council would vote for war. Too many permanent members were benefiting financially from sanctions busting. He stalled and stymied and bluffed it out.

Oliver Twist

I watched another DVD over the weekend, Polanski's Oliver Twist. Apart from Ben Kingsley as Fagin and Edward Hardwicke as Mr Brownlow, most of the actors were not well known.

I guess the best known version of the book is Lionel Bart's Oliver!, the musical version and an altogether sunnier approach than this. The classic David Lean/Alec Guiness version is the best reviewed. Then there was a TV version written by Alan Bleasdale(co-production between Carlton and WGBH/Boston) in which he wrote a back-story based on some hints in the last chapter of the novel. That version had some well known TV actors in Robert Lindsay, Lindsay Duncan, Julie Walters and Michael Kitchen. Alan Armstrong turned up in both this version and Polanski's though playing different parts.

The Alec Guinness Fagin is such an immense characterization that it must intimidate anyone trying to perform a new version. They tend to go for gimmicks - music, a new back-story - in order to breathe some freshness into such a well known story.

Does Polanski succeed? Not really. Kingsley follows the Guinness path and even has a bit of Ron Moody about him, but nothing original. Nancy is less sympathetic than Shani Wallis makes her in Oliver! Jamie Foreman does not seem as evil as Oliver Reed. One interesting fact - the actor who played Sykes in the TV version was Andy Serkis. Yes Gollum! and King Cong!

I was under 10 when I first saw the black and white version in the cinema. I doubt I will ever find a better one.

Forgiveness again

Azalias are out and so are the tulips. Blue periwinkle flowers are creeping over the flower beds and buttercups on the compost heap. Spring is really here.

I spent the afternoon repairing window frames. Nasty blisters had begun appearing in the paintwork. Sanding down the paint I found that those expensive decorators who did the job last time had not prepared the wood properly. It needed paring down to bare wood, cutting out areas of wet rot, treating with hardener, filling with a special filler and sanding down. I did about half the job in 6 hours. Interruptions came in the form of a dish cloth jamming the waste disposal unit and the boiler blowing out. Such are the joys of being a house owner.

But I had a reply from Ben Witherington on forgiveness. Readers interested in religion might try his site at http://benwitherington.blogspot.com/ . He says that we are commanded to forgive in the Lord's Prayer - forgive us our trespasses as we forgive those who trespass against us. Although forgiveness has to be accepted for the deal to be done, that is beside the point. It is our job to offer it. I think he is right.

So, decorators everywhere: I forgive you.

Pride and Prejudice

Two films in a day! This evening I watched Pride and Prejudice in DVD. I did not think that the Colin Firth BBC version could have been bettered, but the recent Keira Knightley version equals it. It is much faster paced and it does suffer from the modern blight of music that is too loud for the voice track, but the design was excellent and there were many strong performances.

I preferred Barbara Leigh-Hunt's Lady Catherine to Judy Dench's and Bernard Hepton's Mr Bennett to Donald Sutherland's, but Keira Knightley and Rosamund Pike were quite stunning as the older Bennett girls. I was surprised how well Matthew MacFadyen did as D'arcy; quite as good as Colin Firth.

When I saw that Knightley had been nominated for an Oscar, I was sceptical. She was dreadful as Lara in the TV version of Dr Zhivago, and simply eye candy in Bend it like Beckham, Pirates of the Caribbean and King Arthur, but in this she shows that she can really act.

Nixon

When I first started as a hematologist I had so little to do that I used to got to the movies in the afternoon. Business soon built up and for most of my career I have too much work. Now in semi-retirement I occasionally have time to put on a video in the afternoon, so while my wife was watching a wartime drama by Noel Coward starring John Mills, I sneaked off into teh other room to watch Oliver Stone's Nixon.

I can understand why Anthony Hopkins was nominated for an Oscar for this performance. He is seldom of the screen, and gives a tremendous exhibition of acting. This is not mimickry; he does not look at all like Nixon, but he captures the man behind the face. To do the part justice demands an actor reared on the Shakespearean stage. He makes Nixon into a figure not too distant from Macbeth. I would have thought it were impossible to make Nixon at all sympathetic, but Hopkins turns him into a figure of tragedy by revealing the greatness in the man that was hidden by compromises with integrity that he made while climbing the greasy pole. History will judge hime more kindly than his contempories, says one character. It depends on who writes the history, quips back Nixon.

The movie, alas was not as good as the performance. It needed a better writer.

micro RNAs

Now this is not for the faint-hearted. If it's too technical read the one about Irish politics instead.

In my lab we have been working on 13q14 longer than anybody else. My colleague David Oscier gets the credit for this. He published a paper detailing the first report of deletions at this site in hematological malignancies. It is not only important in CLL, but it also the most important chromosomal abnormality in multiple myeloma as well. He also found the deletion in some cases of myelofibrosis. (Fitchett et al Cancer Genet Cytogenet. 1987 24:143-50).

The chromosome lab that he set up was the first to regularly get good results with conventional karyotyping in CLL so that the original paper demonstrating that del 13q was a good prognostic feature in CLL and that there was a hierarchy of prognoses depending on the karyotype was largely composed of his patients (Juliusson et al N Engl J Med. 1990 323:720-4).

He isolated the bit of chromosome 13 that was always missing and sequenced the length of DNA that was missing. He also identified the genes that are represented on this missing piece of DNA. (Hawthorn et al Oncogene. 1993 8:1415-9. Chapman et al. Oncogene. 1994 9:1289-93. Liu et al Oncogene. 1997 15:2463-73) .Now here's the rub. Everybody expected the mechanism to be that of the classic tumor suppressor gene.

Retinoblastoma (which is also located at 13q14) is the classical example. This is a tumor of the eye in children that is caused by the loss of the Rb1 gene from both chromosome 13s. Usually the child inherits one mssing or damaged Rb1 gene from one parent and loses the other in childhood. Loss of both tumor suppressor genes allows the tumor to grow, but while there is one still intact, there is no tumor.

It was expected that there would be another gene at 13q14 that acted in a similar way to cause CLL. Although some CLLs do indeed have a deletion on both chromosome 13s, this is not the common finding. Never mind, we thought, although the other gene is there, when we sequence the area we will find a crippling mutation on the other chromosome. There are not many genes in this area. Depending on how you count them there are no more than 5, and possibly as few as two, so it was not going to be difficult to find a mutation. To cut a long story short there were no mutations, nor were there any epigenetic mechanisms like aberrant methylation that would account for both chromosomes not working (Corcoran et al Blood. 1998 91:1382-90. Kapanadze et al FEBS Lett. 1998 426:266-70. Grand et al Genes Chromosomes Cancer. 2004 40:78-83).

I guess people began to think that a small lab like ours had made a mistake, but the really big labs like Carlo Croce's and Ricardo Dalla-favera's confirmed David's findings.

Then Croce reported on microRNAs (miR). miRs are small lengths of single stranded RNA that are able to bind to messenger RNA to prevent its being translated into protein. They are part of the normal control system which allows cells to express or not express particular genes. In CLL Croce found that two miRs, miR-15a and miR-16-1, which are normally located at chromosome 13q14.3, are down-regulated in about 65% of patients (Cimmino et al PNAS 2005 102:13944-9).

The messenger RNA that these miRs target is the one that codes for bcl-2. They normally help to switch off bcl-2 production.

Bcl-2 is one of the complex series of proteins that controls apoptosis or programmed cell death. It happens to be one of the most important inhibitors of apoptosis. It is very important in the functioning of B cells. During an immune response against a foreign germ it is necessary to make a lot of antibody, and the right antibody at that. A process of rapid somatic mutation takes place in lymph nodes and spleen, as genes are shuffled and mixed, altered and corrected so that the appropriate antibody is made. This is a random process and a lot of nonsensical or even harmful antibodies are made. It is very important that the cells makeing these antibodies are killed. They don't need any bcl-2 around preventing that; hence the miRs to switch it off. However, the good antibody producing cells need to survive, and in them bcl-2 needs to be upregulated - but only for a while; when the germs have been dealt with we need the cells used in the immune response to die back, so the bcl-2 has to be switched off. Transgenic mice have been made in which the bcl-2 gene is always switched on. These mice grow huge lymph nodes and spleens - not because they have tumors, but because their lymphocytes are immortal and they bkeep accumulating.

Of course in CLL the lack of these specific miRs to switch off bcl-2 means that the CLL cells don't die properly either.

I am writing about miRs because of a paper that appeared recently in Cell. This concerns miR223 (yes there are a lot of them). Acute promyelocytic leukemia (APL) is quite a rare leukemia (sometimes called M3) where the leukemic blasts begin to mature but get stuck at the promyelocyte level. It is important because most patients get disseminated intravascular coagulation, and used to bleed to death. These patients almost always have a chromosomal transocation between chromosome 15 and 17 (t15;17) which puts the APL gene next to the RAR gene. It was a Chinese discovery that these patients respond well to a form of vitamin A known as all trans retinoic acid (ATRA). Treatment with ATRA has revolutionized the outlook for APL patients, and now it is one of the best types of acute leukemia to have, if you have to have leukemia.

In the Cell paper (2005; 123:819-31), Farzi and colleagues from Rome describe a series of experiments that help to sort out how ATRA works and what the function of vitamin A is in the normal development ofwhite cells. There are two transcription factors that compete to bind the promoter of miR223, NFI-A and C/EBPalpha. These two factors have long been known to regulate the growth and differentiation of many cell types.

This is how they interact. NFI-A keeps miR223 at low levels, but when ATRA is added the NFI-A is replaced by C/EBPalpha. miR223 the suppresses NFI-A. In APL, introduction of the gene for miR223 so that the miR is expressed cause the cells to overcome the block in diferentiation, while knocking out the miR223 blocks their ability to differentiate in response to ATRA. Some cases of APL become resistant to ATRA, and an understanding of this mechanism offers a way forward.

These microRNAs have allowed us a greater understanding of the regulation of genes and it would not be difficult to think of how small molecules could be adapted as drugs for more precise management of leukemias.

Irish politics

The British and Irish governments have given the Northern Ireland politicians a deadline of November 28th this year to form a government of national unity or else they will draw a line under the Good Friday agreement. Hard to believe that the parties will do so. The Good Friday agreement was negotiated by the moderate Ulster Unionists and SDLP parties. Despite being endorsed by a majority of the Norther Irish electorate, that same electorate has turfed out the moderates and voted for the hardline Democratic Unionists and Sinn Fein, who won't even sit down in the same room as each other, let alone form a government together. The DUP say the republicans' claim to have give up the war is bogus. They point to the huge bank robbery last year, the murder of Robert McCartney and now the execution of the English spy, Dennis Donaldson as evidence that the republican movement is one huge criminal conspiracy

It doesn't bode well for a united government in Iraq.

Chucking out memories

How hard it is to throw things away!

Today we have been in the garage clearing up all those things that were carefully stowed away just in case we might need them again.

First it was necessary to get up in the garage loft to dispense with the things we had put up there last time we cleared out the garage. So out went some decorative glass shelving, a broom handle, an old snooker cue with a chip in it, an underwater pump from when we had a pond, my waders with perished rubber from when we had a pond, baskets for planting water lilies (from when we had a pond), hundreds of old flower pots, the remnants of hanging baskets, a pair of dumb-bells, a game of Scrabble with pieces missing, a net for chipping golf balls into, various bicycle pieces including a tire and inner tube, some gears and brakes and a pedal or two, a half-used box of pre-seed lawn fertilizer and seven plastic imitation Grecian urns that were used as plant holders.

Elevated from the garage to the loft went a host of children's garden toys. Pedal cars, see-saws, tricycles, bicycles, wheelbarrows, space-hoppers, paddling pools, sand trays, scooters - throwing those away will be a lot harder. Perhaps the grandchildren will use them when they come to stay.

When I last threw away a few hundred paperbacks I took down the shelving that they were stacked on. Today I removed the wooden shelves from the metal struts, but stored the wood on the perhaps mistaken ambition of floor-boarding the house loft someday.

Then all the discarded rubbish, together with cardboard and polystyrene packing was bagged up, put in the back of the station wagon and taken to the recycling center.

A good day's work and much tidier, but only half the job done. Nostalgia and memories have halted the process.

Outcomes in clinical trials

A recent paper in the New England Journal of Medicine has given us all something to think about. It did not concern CLL; rather it was about a similar disease, multiple myeloma.

Myeloma, like CLL, is an incurable disease of B cells. It has a rather worse prognosis than CLL, but like CLL it has a forme fruste Monoclonal Gammopathy of Undetermined Significance (MGUS) that fits alongside Monoclonal B cell Lymphocytosis.

For those who can take it, standard treatment is an autologous stem cell transplant. This treatment has been pioneered at Little Rock, and where one is good two may be better. Little Rock now propounds the virtue of two successive autografts. There is evidence that, if you can stand it, two are better than one, although some of the evidence is conflicting.

When the patient relapses what is there to do? It turns out that thalidomide will rescue more than a third of patients. If thalidomide is so useful why not add it in at the beginning and continue as long as possible? This was the trial reported in NEJM. A comparison between thalidomide all the way through or only later. Sure enough, patients receiving thalidomide had a greater number of complete remisions and longer lasting remissions, but unfortunately the overall survival was no better. The only difference was that they had to suffer the side effects of thalidomide throughout their illness: tiredness, peripheral neuropathy, constipation and venous thrombosis.

In chronic diseases like myeloma and CLL, trialists have been reluctant to look at overall survival as the end point of trials because it takes so long to get an answer. Instead, surrogate endpoints like remission rate and progression free survival are chosen. It suits pharmaceutical companies because if they wait 15 years for overall survival their patent will have run out before they are allowed to sell the drug.

In the recent CLL4 trial in the UK comparing Fludarabine with Fludarabine + cyclophosphamide (FC) with chlorambucil, FC gave the highest response rate and the longest progression free survival; but the overall survival for the three arms is so far not different. The same is true of the German F v FC trial.

If you look at the chlorambucil arm pf CLL4, which has remained the same in UK trials since the 1970s, there has been a progressive improvement in 5-year survivals over that time, from 46% to 62%. Part of this might be ascribed to better supportive care, antibiotics, growth factors, platelet transfusiohns and the like, but the most important factor has been the availability of a different drug to use when the patient relapses, namely fludarabine. It has been suggested that there will never be a difference in overall survival in CLL4 because it will be possible for the chlorambucil patients to crossover to FC or even FCR.

The immediate answer is why not? We are not playing a game that has to be fair for both sides. We are seeking the best treatment strategy for patients. There will be some patients who will be fine on chlorambucil, who may never need to be put at the risk of fludarabine immunosuppression. For the rest, if the risk of relapse is allayed by certainty of a response from FC or FCR why not have two bites of the cherry. Of course , the best trials would compare treatment sequences.

Global warming

It certainly hasn't reached Bournemouth yet. Although bright and breezy you need a coat to go out today. But it got me thinking about how much humans can do to alter the climate. I am well aware that the vast majority of scientists believe that greenhouse gasses are to blame for changes in temperature and that natural disasters like Hurricane Katrina are laid at the door of gas guzzling SUVs. But is the evidence convincing? (For a different view of global warming go to http://www.co2science.org)

The scientist in me is wary of stuff that makes headlines in newspapers. Publicity equals money for scientists and scare stories sell newspapers. Hardly anything that is reported in the press about science is accurate. It is oversimplified, sexed-up, exagerated and always I hear someone cranking the handle of self interest.

Two things make me wary. First is the short obervation period. We know that climate does fluctuate. In Roman times there were vinyards in Britain. In the 17th century the River Thames froze over. Although a graph of the rates of fluctuation could be constructed and a varying rate of change could be measured, I suspect that it is too soon to work out whether the change is a temporary blip or a permanent one.

Second is buffering. All systems seem to have a built in homeostatic control. In the human body, for example if the blood gets too acid we start breathing heavily to blow off carbon dioxide which raise our pH. If carbon dioxide levels in the atmosphere rise then plants are encouraged to lay down carbohydrates by photosynthesis. There is a huge reservoir of blue green algae in the Pacific Ocean that is blooming becuase of raised carbon dioxide. Now whether this sort of buffering is or will exert a corrective effect I do not know, nor do I know of anybody working on it.

I can see that there is a case for reducing polution in the atmosphere. Since burning of coal was abolished in Britain it is a much cleaner place and chest infections are fewer. It is clearly technically possible to obtain energy in a less polluting way, and it is technically possible to stop being so profligate in our waste of energy. At the moment our reason to do so is to respond to the propaganda that governments and NGOs pepper us with. It won't work. We won't believe that governments are serious unless they make it economically advantageous for us to conserve fuel. A massive hike in the tax on gas would do it. A concerted effort to raise the tax on air travel would do it. Tax breaks for nuclear power or clean coal technology would do it.

The current fashion is for hybrid vehicles. These cars that run on petrol on long runs but swich to electricity in towns are encourages by tax rebates, low road fund licenses, and freedom from the London congestion charge. However, we should ask ourselves rather whether we really need a new car. The environmental cost of building one is greater than teh environmental savings from running one. The world would benefit more from having one fewer car factory than from a slightly greater mpg. A far better buy would be a second hand diesel BMW. They will match the mileage of a Toyota or Honda hybrid, last for 200,000 miles and run on old cooking fat when the oil wells run dry.

Spring at last

Sunshine, balmy breezes, flowers everywhere, wagtails and blue tits, men in shirtsleeves, buds, blossom; it's here.

A full house with three of the children home for dinner with their respective boy friend or girl friend, and only last weekend we saw the fourth with his family. All is well with the world.

No April fools!

Steroids 2

Steroids and the immune response.

If you get put off by technical language you should skip the next three paragraphs.

Corticosteroids acts through intracellular receptors, which are present in almost every cell in the body. The receptors are present in the cytoplasm of the cell often bound to the chaperoning protein HSP-90 (remember that from ZAP-70?). On binding the steroid the receptor is freed from the HSP-90 and this exposes its DNA-binding region. The steroid-receptor complex then crosses the nuclear membrane into the nucleus and binds to DNA. It has been estimated that the expression of as many as 1% of all genes is regulated by the steroid receptor, which accounts for the multiple effects of the hormone.

In general pharmacological doses of steroids are anti-inflammatory. They suppress the production of a number of inflammatory cytokines such as IL-1, TNF-a, GM-CSF, IL-3, IL-4, IL-5, IL-8, as well as prostaglandins, leukotrienes and adhesion molecules, but the production of other proteins such as endonucleases and lipocortin-1 is increased.

Of all the cells in the immune system, macrophages are the most affected. Normally they
home to sites of inflammation and take part in antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC). Corticosteroids down-regulate the expression of Fc and C3b receptors on macrophages and reduce the secretion of pro-inflammatory cytokines and eicosanoids. Expression of class II histocompatibility molecules is reduced, which in turn inhibits antigen presentation. Expression of adhesion molecules is inhibited, which reduces cell-cell interactions.

So what does all this mean? Steroids are used first and foremost to quieten down inflammation. In diseases like rheumatoid arthritis the pain and swelling heat and redness of the joint are all calmed down by the use of steroids, but there are lots of other diseases where a similar process is going on with macrophages acting in concert with antibody. Patients with CLL will know all about autoimmune hemolytic anemia and immune thrombocytopenia. In both of these an antibody kills the affected cell with the help of a macrophage. Steroids work in these conditions, not by getting rid of the antibody, but by paralyzing the macrophages. But there is a corollary for CLL patients. Antibodies like rituximab rely on macrophages to help them kill the CLL cells. If steroids are given with the antibody, they are likely to lessen their effect.

Another major effect of steroids is to quieten down allergic reactions. This is where those difficult words leukotrienes and eicosanoids come in. The eicosanoids are a family of locally active hormones derived from the twenty carbon fatty acid arachidonic acid. Most members of this family have roles in inflammation, including regulation of vasodilatation, vascular permeability, pain and the recruitment of white cells. The eicosanoid family includes prostaglandins, thromboxanes, leukotrienes and prostacyclins. Leukotrienes cause smooth muscle to contract, increase the permeability of blood vessels and stimulate the secretion of mucus. You can see how this would be involved in asthma, and, of course, steroids are the most useful drugs in treating asthma.

The thromboxanes and prostacyclins as well as being involved in inflammation are important in clotting via the platelets and the blood vessel walls. The synthesis of the prostaglandins involves enzymes known as cycloxygenases often abbreviated to Cox. The recent anxiety over Vioxx related to its role as an inhibitor of Cox. There are very many inhibitors of cycloxygenases – they include drugs like ibuprofen and diclofenac. These drugs have unwanted side effects, particularly bleeding from the stomach. Because of this pharmaceutical firms have tried to inhibit different forms of the enzymes separately. Inhibiting Cox-2 rather than Cox-1 should avoid the bleeding problems. Unfortunately it looks as though this increases the risk of thrombosis.

As well as their effects in quelling inflammation, steroids also have effects on lymphocytes. In T cells, particularly early in their life span, steroids induce apoptosis, although this can be stopped by certain hormones like prolactin, or by signaling trough the T cell receptor or by 17-AAG. B lymphocytes also can be sent into apoptosis by steroids, though again they are more resistant later in their development.

All in all treatment with steroids suppresses inflammation in many and varied ways and also has a rather unpredictable effect on specific immunity. This means that patients on steroids may have their primary disease quelled, but at the same time they become susceptible to infections. The most likely infections are fungal, some bacteria such as TB and viral. More than this, the normal response to infection – fever and feeling unwell – may be absent so a patient may get very sick without the tell-tale signs being noticed.

So the side effects of steroids begin to add up. Diabetes, high blood pressure, thinning of the bones, shape changes of the face and body, fluid retention, acne, striae, muscle wasting, psychological changes and now infections; powerful drugs they may be, but most doctors are reluctant to use them except in short courses.

PLL

There has been a bit of discussion about transformation of CLL to PLL. I have been saying that it doesn't happen. This has caused some confusion, so let's see if I can straighten things out.

Prolymphocytic leukemia is quite a different disease from CLL. It has bright surface Ig, it is CD5 negative, CD23 negative, FMC7 positive, CD22 positive and it has more than 55% prolymphocytes on the blood film. Often there is a paraprotein and while the spleen is enlarged, the lymph nodes are not. It is also very rare. I have 7 cases on my books, compared to over 800 CLLs.

Most of the confusion arised from a condition known as CLL/PLL. This condition has between 15% and 55% prolymphocytes in the blood but the cell markers are those of CLL, not PLL. In the 1980s the FAB group (nothing to do with the fab four, it stands for French-American-British) having divided up the acute leukemias and MDS, decided to have a go at the chronic lymphoproliferative disorders. They divided up CLL into typical and two types of atypical CLL. One sort of atypical CLL was CLL/PLL. In a big series of patients, my group and Danny Catovsky's group demonstrated that there was a close correlation between atypical CLL and trisomy 12.

Although people talk about prolymphocytoid transformation of CLL, which seems to imply increasing numbers of prolymphocytes over time, this does not really happen with trisomy 12. There are variable numbers of increased prolymphocytes, but this is a pretty permanent state. I followed one such woman for 20 years with no change in the percentage of prolymphocytes. She had a big spleen, a high white count, a paraprotein, but CLL type cell markers and mutated VH genes. She was non-progressive. If we go back to the papers in Brit J Haem by Junia Melo and David Galton that described CLL/PLL we find that this is just what they descibed.

Here is a section of a paper that I wrote which reviewed the Melo papers:

"Contrary to the common perception, in a study of 55 cases of CLL/PLL half showed a stable picture without a progressive increase in prolymphocytes. The prognosis of this group was similar to that of stable CLL without prolymphocytes. In one third of cases the increase in prolymphocytes was unsustained and in only 18% was there a definite progression towards a more malignant phase of the disease."

In other words a third of patients had a transient increase in prolymphocytes - perhaps triggered by infection or vaccination, and only 18% had a real prolymphocytoid transformation to a more malignant phase. 18% of 55 is 10 cases.

So what was going on with these 10? Trisomy 12 is not the only chromosomal abnormality found in atypical CLL. The very rare t(14;19) translocation involving bcl3 has an excess of prolymphocytes anda poor prognosis. But 80% of patients with p53 mutations or deletions also have atypical morphology. P53 aberrations are likely to occur as a form of chromosomal evolution, and are associated with an increased aggressiveness. I have certainly seen this effect. But note this is not prolymphocytic, but prolymphocytoid transfomation. The cell markers remain typical of CLL.

Part of the confusion lies in the rather atypical immunophenotype of trisomy 12 cells. The surface Ig is rather stronger than normal in CLL and CD20 is also stronger. FMC7 is also moderately positive. These markers have a superficial resemblance to those of PLL but they are quite distinct.

Just to confuse matters more, a minority of PLLs are CD5 positive. We published a paper from my group and the French group from Nantes which exposed these as a variant form of mantle cell lymphoma. They are not the blastic form of MCL that has been described previously, but what appears to be PLL with mantle cell markers including the cyclin D1 and the t(11;14) translocation. They have a dreadful prognosis on the whole.

Is everybody thoroughly confused? Well that's better than being so sure of yourself that you treat zebras like white horses that have caught the sun behind prison bars.

Chauvinism

Arsenal 2 Juventus 0. A masterly display by the London soccer team left the team from Torino reeling as the Italians had two men sent off for foul play in the last five minutes. Such was the speed and movement of the former English Champions that the Italian league leaders resorted to ugly lunges and wild kicks as the Arsenal forwards sailed by them. A real triumph for England.

Except that there were no Englishmen in the London team. Plenty of players from France and Spain and the Ivory Coast, and one from Germany and one from Holland and even one from Belarus. The coach, too, is French. Mind you, the Torino team only had four Italians.

It got me thinking about our laboratory which contains Chinese, Russians, Iraqis, Jordanians, Egyptians, Mexicans, Canadians, Australians, Belgians, Dutch, Germans, Italians, Irish, Indians and Pakistanis. Any achievements will be credited to the Welsh charity that supports us.

If you go into the Jardin des Plantes in Paris through the entrance nearest the Gare d’Austerlitz.you will see a statue of the “Father of Evolution”. How generous, I thought, of the French to so honor an Englishman. But the statue bore not the bearded visage of Charles Darwin, but the bewigged features of Jean Baptiste Pierre Antoine de Monet Chevalier de Lamarck, the Frenchman who went down the blind alley of inheritance of acquired characteristics.

Chauvinism meaning “bellicose patriotism” derives from Nicolas Chauvin a highly decorated veteran of Napoleon’s army, and the French are particularly good at it. You can read about him at http://www.chauvin.org.uk/story.htm .

We often hear arguments about the superiority of this of that economic system and this or that health service. I remember president Clinton trumpeting American achievements in science. He included in his list the splitting of the atom, which every school child knows was achieved at the Cavendish laboratory, Cambridge (that’s England not Massachusetts) by Sir Ernest Rutherford, a New Zealander.

Now New Zealand has a lot to feel chippy about. Apart from Rutherford there is a whole list of famous New Zealanders who are generally assumed to come from somewhere else, especially (perish the thought) Australia. The first man to climb Mount Everest, Sir Edmund Hillary, was from New Zealand. Film directors Jane Campion and Peter Jackson (remember Lord of the Rings) as well as actors Sam Neill and Anna Paquin are well known. Golfers will know Bob Charles, the left-hander and Michael Campbell, and equestrians, Mark Todd. Kiri Te Kanawa is one of the world’s greatest opera singers. The first surgeon I worked for, Harry Espiner, was a New Zealander and so are Myf Spellerberg and Adrian Copplestone who appear as a co-authors on some of my papers. Bruce Maclaren founded the Maclaren racing car company, Ngaio Marsh is a well known author though Katherine Mansfield is more important. Jack Lovelock was the first record breaking runner, but he was followed by Peter Snell, Murray Halberg and John Walker. William Pickering from Wellington was the man behind America’s first space satellite, Explorer 1. Keith Park, the RAF commander at the Battle of Britain was from New Zealand, as was Charles Upham, one of only three soldiers to win the Victoria Cross twice. We all know about Crick and Watson, the discoverer of DNA, but there was a third member of the team who won the Nobel Prize with them. Maurice Wilkins was a New Zealander. Harold Gillies was the maestro of plastic surgery who repaired the burned faces of Battle of Britain fighter pilots. He was from New Zealand. Robert Burchfield, the Editor of the Oxford English Dictionary was from New Zealand. Oh, and Xena, the Warrior Princess is from New Zealand. I believe there is also a promising young actor called Russell Crowe. However, he has moved to Australia, perhaps trying to emulate the actor who appears to be his hero, who hailed from there, one Errol Flynn.

The thing is that many of the above were New Zealanders when New Zealand was a British colony and were this British subjects, as were Oscar Wilde, James Joyce and WB Yeats, though the Irish claim them all. So, of course, were George Washington and Thomas Jefferson before they rebelled. So was Ghandi, whether in South Africa or India. Just as all Pakistanis were once Indians. Thought for the Day this morning on Radio 4 was taken from the Hindu scriptures and warned us of the danger of assuming that we all see things from the same viewpoint. The speaker also warned us about assuming that today’s historical assumptions applied when the events were taking place. I am sure Keith park thought of himself as both British and New Zealander. To suggest that Paul Revere’s message was “The British are coming” is crass. They were all British at the time. His message was “The regulars are out” or something similar.

It is an interesting question of where we get our drugs from. Monoclonal antibodies, for example, were developed by an Argentinean and a Swiss working in a British laboratory and funded by the British government which declined to patent them, reasoning that such a discovery should be for the whole world. The development of rituximab began with an Australian working in a British laboratory and funded by a Welsh charity who then passed the idea on to a Californian who also picked up a discovery of a man from Boston. A small biotech company in California was set up to develop the drug which is marketed in the rest of the world by a giant Swiss company.

Campath was originally developed in the same British lab that discovered monoclonal antibodies. It was originally developed and marketed by a British company before that company was taken over by another British company that wasn't interested in developing it further because it was more interested in AZT for AIDS which the first company had also developed, so it was sold to a German company that now markets it in America through its wholly owned subsidiary, but is currently fighting a take-over by the German subsidiary of an American pharmaceutical company.

One of the biggest sellers among drugs is Viagra which was discovered by British scientists working in the laboratories of the British subsidiary of an American company. Chlorambucil is British, but cyclophosphamide was discovered by an Austrian Jew who had escaped to Australia where he was working on a chemical to put a permanent kink in wool. He was invited to England and there pursued an illustrious career in cancer research. He was my friend.

My point is that we shouldn't get too Chauvinistic about scientific discoveries. Science is international and knows no boundaries. Though I sometimes joke that according to the Japanese 55% of all useful discoveries were made in Britain, I have to admit that like Arsenal we have often employed foreign mercenaries, and now that America has more money the mercenaries are playing for America.

Not Spring yet

I won't say Spring has arrived, because it certainly hasn't. But the weather has changed. It is certainly warmer, but not at all pleasant. The wind is strong, the sky is overcast and the rain spits, drizzles, seeps, stops, starts and sets in.

The daffodils are out but bedraggled, the crocuses have fallen over. We have some impressive catkins on the twisted hazel. Today I saw a jay on a leafless branch; a glimpse of tan that first I thought was the remains of last Fall's leaves, but he seemed to be shivering, and surely if the wind were doing that it would have blown away any leaf.

Driving home from Tunbridge Wells last evening was a trial. 20 mph on the M25; four lanes nose to tail; the sky full of grey warnings gradually intensifying as we stuttered along. Driver behavior was very good; no lane hopping or tailgaiting. It was as if we were all in the same boat so we'd better stick together.

Selling Honors

Tony Blair is in trouble. Time was when the funding of political parties was straightforward. The Tories were funded by big business and Labour by organised labour. Corporations are no longer allowed to fund the Tories and the Unions have insufficient funds to pay for New Labour - and in any case New Labour wants to distance itself from the Unions. Both parties turned to rich individuals -but the Labour Government discouraged that by making such gifts public, exposing some Tory donors as tax exiles.

To get round the regulations, both Parties solicited loans, that don't have to be declared, but may never be repaid. But if you loan a million pounds and don't want to be repaid, what do you want?To be called Sir?

A knighthood is all very well if you want to think of yourself dressed up in armour and riding a horse, but a Lordship carries a seat in the House of Lords. When Baron Sausagemaker sat in his country seat and was content to Lord it in the County where he rode to hounds and Lady Sausagemaker entertained the County Set, and the only time he used his vote was when they threatened to abolish foxhunting, it was sort of alright. There was no great threat to the Constitution in buying and selling honours. The House of Lords is the best gentleman's club in London (some say the world); the booze is cheap, the view marvellous and they even pay you a couple of hundred quid for turning up. There is a long tradition; Lloyd George even had a price list: so much for a marquis, so much for a duke. And all those hereditary peers got their gongs by being a crony of Charles the first or the illegitimate son of Charles the second or some other reward for services rendered.

What's different now is that Tony Blair has reformed the House of Lords. Most of the hereditary peers have lost the right to vote, but the newly created ones haven't. They are not just getting a nice restaurant by the Thames, they are buying a vote; instead of being one in 40 million when it comes to having their say, they are becoming one in 600.

Selling honours may sound pretty crass and venial, but it is better than selling influence. Dressing up in ermine and going on parades is pretty harmless. Paying a million to influence decisions or change the law isn't.

So, completing the reform of the House of Lords becomes urgent. The Prime Minister's patronage has to be removed. A major elected element is vital. But if both houses are elected, which will have supremacy? Both can claim electoral legitimacy; the more recently elected will have to win.

The Upper House is supposed to be a Reforming Chamber; somewhere where legislation can be scrutinized and revised. It needs thought and common sense; not emotion. From somewhere it has to recruit experts and the worldly wise. These are not necessarily the skills of politicians.

Spring Tomorrow

No Spring has been as late as this since 1964. Temperatures hover between 0 and 5 degrees Celcius. Going outside requires a scarf, thick gloves and an overcoat. A few straggly snowdrops have appeared and a smattering of draggly crocuses. The daffodills have been tight buds for weeks now. No sign of the grape hyacinths. The ornamental cherry that often flowers in December shows just a faint haze of pinkness on the twig tips. Some days a few Great Tits visit the peanuts hanging from the May tree and we have had one nut attack from a newly awoken squirrel. The grass is yellow-green, but the moss is dying. There are faint white buds on the magnolias. A flame-of-the-forrest has wispy pink flowers, but no red bracts.

But, astonishingly, one camellia is smothered with bright red blooms; a gory gash against the shiny green; a defiant statement of scarlet promise.

Drug trials - what went wrong.

The clinical trials disaster in London has intimidated people from taking part in future clinical trials. A recent poll in AOL indicated that 80% would not take part in a drug trial. It is important to look at what happened.

The drug being tested was a monoclonal antibody directed at a molecule on the surface of T cells called CD28. It is one of the co-stimulatory molecules on T cells. Normally in order to stimulate T cells you need to stimulate both the T-cell receptor (TCR) complex (usually done with anti-CD3 in the test tube) and a co-stimulatory molecule. However, there is a subclass of anti-CD28 antibodies known as superagonists which can stimulate T cells without involving the TCR. They do this by binding to a different site on the CD28 molecule, so that adjacent molecules are lined up in a linear array on the cell surface, which facilitates signaling.

An important property of CD28 stimulation is that it is crucial for the survival and proliferation of regulatory T cells. Regulatory T cells have suddenly assumed a great importance in immunology. They are recognised by being positive for CD4 and CD25 and have a main function in preventing the growth of autoreactive T cells. Mice that lack regulatory T cells develop autoimmune disease. Administration of superagonistic anti-CD28 to mice with autoimmune diseases produces remissions. There is also some suggestion that these T cells have a role in controlling the growth of lymphoid tumors.

In CLL patients with autoimmune disease like AIHA and ITP the regulatory T cells are suppressed. Not only did this antibody appear promising in autoimmune diseases like rheumatoid arthritis and diabetes, but in CLL it might controle AIHA and ITP and possibly the CLL itself.

So what went wrong? One of the problems of stimulating T cells is that they release cytokines. Among these is interleukin-2, which is licensed for the treatment of melanoma and kidney cancer. It is extremely toxic. It cause a high fever, shivering attacks, diarrhea, low blood pressure and makes the patient feel dreadful. So-called capilliary-leak syndrome develops. Fluid leaks from the capilliaries of the lungs, which become waterlogged, so that breathing is difficult. The blood pressure falls so that the kidneys shut down and renal failure develops. Other effects include damage to the liver and bone marrow. The activated lymphocytes visit the heart, so that sometimes heart attacks occur. Interleukin-2 induces the relase of other cytokines - the so-called cytokine storm. To me this sounds like what has happened to these volunteers. Interleukin-2 stays in the blood for 7 minutes. Humanized monoclonal antibodies hangs around for an average of three weeks.

When the anti-CD28 was given to mice there was no evidence of cytokine storm. Mouse CD28 is very similar to human CD28, and the human anti-CD28 cross-reacts with the mouse molecule. As far as I can tell it had been safe also in primates, probably macaques. Nevertheless, in the trial, just to be safe the volunteers were injected with one five hundredth the dose of what was safe in the mouse. No-one was expecting it to be anything other than safe in the volunteers.

Is there any evidence that the trial was improperly conducted? This was a phase I trial intended to test the safety of the drug and to determine a safe dose. Often cancer drugs are tested on patients who are terminally ill who have a slight chance of benefitting from the drug; here a decision was made to use healthy volunteers. In retrospect, using sick patients might have resulted in them all dying of the side effects. The drug was given to eight volunteers with a new volunteer being started every few minutes. This seems foolhardy, but is a common practice. Obviously, had they been injected on successive days the trial would have stopped after one volunteer. But with the background of a safe animal trial behind them, no-one was expecting anything untoward. The volunteers were paid £2000 each. It is not surprising that eight healthy young men felt the risk worth taking. One young man testified in the newspapers that he had paid off his mortgage by taking part in phase I trials.

Does this invalidate the use of animal trials? There is no point in protesting that animals are identical to humans. If that were so there would never be any need to test on humans after a drug has been shown to be safe in animals. Clearly there are diferences. But hundreds of drugs have never been tested on humans because they were too toxic to animals. If the animal tests were omitted there would be many more like the London Six.

My conclusion is that this was an idea with great potential benefit. So far the only criticism that I can make was that they should have staggered the doses so that the side effects would have affected fewer volunteers, but hindsight is fine thing.

Chai Patel

Tony Blair is under fire. As a third term prime minister he is vulnerable. He has already announced that he will go before the next election, so his patronage has diminished. Despite a majority of 70 he is having difficulty in getting his legislation through parliament. This is probably because his agenda is not traditionally Labor.

Britain has a long tradition of preferring well spoken, well dressed, well mannered leaders. Tony Blair, the ex-public school lawyer easily beat the grammar school, Johnny-come-lately, John Major in 1997; but Blair was an anomaly. Previous Labor leaders like Welsh windbag Kinnock, scruffy Michael Foot, Yorkshire pipeman Wilson, did not have Blair's polish, and it is doubtful if anyone other than Blair would have won that election for Labor. In subsequent elections the Conservatives but up their own blunt Yorkshireman, Haigh (who in any case was bald) and the ageing Howard (who was both bald and Jewish). Now they have selected Cameron, a well dressed, well spoken, well mannered Old Etonian who is both younger than Blair and looks it. It takes no crystal ball to recognise that Cameron will walk the next election, especially against the miserable Scotsman Brown, who is respected for his efficiency but liked by virtually no-one.

The cracks in the Labor cause are already appearing. The Labor left are fed up with Blair's middle class values. The education Bill only got through with Tory support and the Health Bill will be attacked for similar reasons. It is unlikely that the Identity Cards legislation will pass unscathed. But before all that we have the tang of sleaze. John Major's Tories were tainted with sleaze. No that's unfair. The Tories were no more sleazy than any other government. It was just that people decided that it was time for them to go. In Blair they saw a better model. Now the same thing is happening in reverse. The focal point at the moment is Chai Patel. He among others lent the Labor Party over a million pounds to fight the last election. The terms of the loan are vague, but it seems apparent that it was a disguised gift. Certainly the Party is in no position to repay the £10 million that they borrowed from him and other donors. They owe more than that to the bank who will not be so forgiving. No, it was expected that after a while the "loan" would be quietly forgotten about. But being a loan rather than a gift it didn't have to be declared to parliamentry scrutiny.

Why would the donors do this? In return they were expecting peerages. Entry to the smartest club in London, and the right to call yourself Lord. It looks good on the Business stationery and the wife likes to be called Lady (though she would settle for a knighthood - she would still be a Lady). It was only when someone queried Chai's fitness to be a Lord that the fiddle was revealed.

I knew Chai in the 1980s. He was a junior doctor in my hospital. He was very good. Smart, organized, efficient, very bright; he rescued one of my acute leukemia patients at a time when we had inadequate antibiotics and poor supportive care. After he left us I heard that he had been headhunted by a major investment company. He had been investing for himself on the stock market while a junior doctor, and made a good profit. He has since made a lot more money by running a chain of nursing homes.

I was sorry to see him the subject of such adverse publicity. I liked and admired him. He is a severe warning to stay clear of politicians. The dirt rubs off.

Steroids 1

Corticosteroids are so called because they are made by the cortex of the adrenal gland. The gland makes a number of steroid hormones. Rarely the gland stops working - in the past it was usually secondary to TB; nowadays it is usually caused by an autoimmune process. People without functioning adrenal glands have Addisn's disease, named after Thomas Addison, a physician at Guy's Hospital in London from 1824 to 1860. Addison was a contemporary at Guy's of Thomas Hodgkin who decribed Hodgkin's disease. As well as hypoadrenalism Addison also described pernicious anemia.

If you lack adrenals you become weak and watery, you lose weight, your blood pressure falls, your muscles waste and you get a low blood sugar. The clue to diagnosis is to look for brown pigmentation of the skin creases of the palm. I remember in the days when doctors did house calls being asked to see a middle aged woman in bed with lassitude because her doctor thought she was anemic. A glance at her skin creases made the diagnosis for me and made me some sort of genius in the eyes of her doctor. I have to confess to missing the diagnosis in my next door neighbor. She became increasingly suntanned and all I could think of was how they could afford so many foreign holidays.

What is lacking in Addison's disease are the adrenal hormones, cortisone and aldosterone. Cortisone is called a glucocorticoid, because it particularly affects blood sugar, and aldosterone a mineralocorticoid because it controls the balance between sodium and potassium in the body, causing sodium retention and potassium loss by the kidneys, and thus affecting the blood pressure - if you don't have enough of it your blood pressure falls and if you have too much of it your blood pressure rises. Although cortisone is mainly a glucocorticoid it does have some mineralocorticoid effects.

Too much cortisone production is known as Cushing's syndrome, though strictly speaking this should refer only the the form that is caused by the production of too much adrenocorticotrophic hormone (ACTH) by a pituitary tumor. Harvey Cushing, perhaps the greatest of neurosurgeons, was an American pioneer first at Johns Hopkins and later at Harvard with an interlude at Oxford with Sir William Osler. He died of a heart attack in 1939 at the age of 70.

In Cushing's syndrome there is typically a moon face and a change in body shape. A 'buffalo hump' is part of a round body, but the arms and legs are spindly. The shape has been describes as a 'lemon on matchsticks'. The muscles are wasted and weak, the skin is thin with stretch marks, there is often blleding into the skin. The bones become weakened with crush fractures of the spine. Often the patient becomes diabetic as the blood sugar gets out of control and the blood pressure may also be high. Sometimes there are masculizing effects becuse the adrenals also make a certain amount of testosterone, and this is probably the reason for the rise in hemoglobin. Finally the brain is also affected with inability to sleep, enormous energy, emotional lability, and even psychosis.

This disease is important because although Cushing's syndrome is rare, when steroids are used in treatment the side effects are the same.

The adrenal gland makes cortisone, but it is converted in the liver to hydrocortisone. The relationship between prednisone and prednisolone is the same. Today neither cortisone nor prednisone is much used, we use hydrocortisone and prednisolone almost exclusively. In Addison's disease replacement of the missing steroids requires 20 to 30 mg of hydrocortisone a day given in a divided dose morning and evening with the larger portion in the morning because that is how the body manages it. We need a big dose of steroids to get us out of bed in the morning. To replace the missing aldosterone a small dose, 50-300 micrograms, of the mineralocorticoid, fludrocortisone, is given.

Hydrocortisone is also used intravenously in acute situations like shock or asthma, but generally most people requiring treatment have prednisolone for small to moderate doses and either methylprednisolone or dexamethasone when larger doses are needed. This is because prednisolone has less mineralocorticoid activity (and therefore less fluid retention) than hydrocortisone and dexamethasone less still. Betamethasone and Beclametasone have very high topical effects without being absorbed systemically and are therefore often used on the skin or in the lungs (as an inhaler).

It is important to recognise the dose equivalants for the various types of steroids.

20 mg of hydrocortisone is equivalent to 5 mg of prednisolone is equivalent to 4 mg of methylprednisolone is equivalent to 750 micrograms of dexamethasone.

Expert Witnesses

I have spent most of the day working on a report for a medico-legal case. I feel sorry for the poor woman who has had her life spoiled by a mishap during her first pregnancy. She suffered a rare complication of pregnancy that was nobody's fault. It was treated as well as it could be in the 1970s, but she was left with a disability that has persisted. A couple of years ago she suffered an exacerbation of her original problem so that the resulting disability got worse. My role in this as an expert witness was simply to dismiss a red herring that someone had raised as a possible cause.

Reading through the whole thing it seems to me that there is no reason to blame anyone for what happened. Everyone acted throughout according to the guidelines available at the time. At least some of the deterioration can be put down to the patient's lifestyle choices, but I doubt whether she made those choices with any inkling of the likely outcome. I guess she is looking round for someone to blame for her predicament and her doctor was a likely candidate.

Patients sometimes have unreasonable expectations of modern medicine. Such are its successes that it is expected always to come up with the goods. But life doesn't work like that. Even if doctors did the right thing every time patients would still die. And no-one could expect doctors to do the right thing every time. To err is human. The standard by which British doctors are judged is would an ordinary doctor (not an expert or specialist) be expected to act in a different way. We are judged against our peers not against the best.

Being an expert witness is a hazardous business these days. Professor Meadows was struck from the Medical Register for misleading the court because of his misunderstanding of statistics in the Sally Clark case. He has now been re-instated and the judge had harsh words for the Disciplinary Committee of the General Medical Council. Doctors had been deterred from acting as expert witnesses for fear of making a mistake. It seemed to me that it was the court that had made the mistake, not the witness. In an adversarial system an expert witness gives what he thinks is the correct interpretation of the evidence. If the opposition thinks he is wrong then they put up another expert to refute what he says. If Meadows' statistical error was so childish, why did nobody dispute it at the time?

Regulations

About the curdled clouds
The careless kiwis fly
Above the jostling crowds
That watch the hopeful sky.

Unknown the ban on flight,
Aerodynamic too;
They never hoped they might;
They simply went and flew.

Forgiveness.

A Church of England vicar has resigned because she cannot forgive the London 7/7 bombers who murdered her daughter.

Should a Christian always forgive? A simple reading of the Bible shows that it is not so. Universal forgiveness is a modern heresy. In John 3:16 we are told that God so loved the world that he gave his only begotten son that whosoever believes in him should not perish but have everlasting life. Universalists emphasize the fact that it is the whole world and major on the 'whosoever'; but it should be noted that this forgiveness is conditional. The words 'believes in him' are not decoration; they are the condition. Two verses later it says, "he who does not believe is condemned already."

In I John 1:9 we learn, "If we confess our sins he is faithful and just to forgive us our sins and to cleanse us from all unrighteousness." Note the condition: 'if we confess our sins.'

On the cross Jesus said, "Father forgive them for they know not what they do." Was this a prayer for all mankind or merely for the soldiers who were carrying out the crucifixion? You only have to read his confrontations with Herod and Pilate, Annas and Caiaphas to realise that they knew what they were doing. Caiaphas was the one who had advised the Jews that it would be good if one man died for the people. (John 18:14) They at least were not included in any general forgiveness. And what about Judas? We are told that the devil entered into him.

Jesus tells us to love our enemies and to pray for those who persecute us. Paul expands on this in Romans chapter 12. He tells us to bless those who persecute us. We should not repay evil for evil. We should not take revenge. He quotes from Proverbs chapter 25, "If your enemy is hungry, feed him; if he is thirsty, give him something to drink. In doing this you will heap burning coals on his head." In other words doing good to one's enemy might bring him to repentance.

In the parable of the unmerciful servant the man who had been forgiven a great debt is condemned when he fails to forgive the smaller debt of a fellow servant (Matthew 18:21-35). But note verse 29: his fellow servant fell to his knees and begged him, "Be patient with me, and I will pay you back." This story exorts us to forgive those who beg forgiveness, for we have been forgiven much more.

Forgiveness is available for everybody. "While we were still in our sin, Christ died for us." (Romans 5:8) There are countless exortations for brother to forgive brother. Those who have placed themselves under the covenant of Christ have an absolute obligation to forgive others under the same blanket. But those who reject the love of God and his priceless gift of grace put themselves beyond forgiveness.

Even if we are able to overcome our own grief and for our own benefit are able to come to terms with the hurt that has been done to us - and this always takes time and prayer - the perpetrator remains unforgiven because God's forgiveness is conditional on repentance. Forgiving those who do not repent does no good. It only encourages them to go on sinning.

Suicide bombers remove themselves from the possiblity of forgiveness. Man is destined to die once and after that to face judgement. (Hebrews 9:27) What they did in London was unspeakably evil. It cannot be forgiven and the bombers are beyond forgiveness. It is absolutely right for a Christian to hate evil. A bereaved mother can sympathize with the mothers of the bombers that their children should have been lost to them; she can pity the fact that they were led astray by evil men; but of their own volition they did this evil thing and then removed themselves from the possibility of repentance. There is now no-one for her to forgive. What remains for her is to cleanse her soul of bitterness. It's not easy. Who can say that they would not feel bitter in such a situation? But it is certainly true that when the bitterness goes she will be healed.

Physician assisted suicide.

This evening I attended a seminar on physician assisted suicide. Lord Joffe's Bill is due to be debated in the House of Lords in May.

I am against the Bill for the following reasons:

It negates what doctors are there for. I went into medicine to save lives not to dispense with them. Although there would be an opt out clause for concientious objectors, the Bill would fundementally change the relationship between doctors and their patients.

It underestimates the ability of palliative medicine. The Hospice movement begun by Cicely Saunders (whose Memorial Service in tomorrow in Westminster Abbey) has had remarkable success in aleviating suffering. there is no reason why anybody should be in pain.

It is a slippery slope. In 1967 I fought a losing battle against the Abortion Act. The propaganda told us it was to prevent back-street abortions of which there were supposedly 100,000 a year. When the Bill was enacted the British birth rate fell by the number of legal abortions. How could it have done do if it was simply replacing the back-street abortions? In fact today 20% of all pregnancies end in legal abortions; virtually none because the life of the mother is threatened; virtually none because the mother has already had 7 pregnancies and she can't manage an eighth; virtually all because it is not the woman's choice to have a baby now. Once the door is open a chink, experience tells us that it will be forced wide open.

It is not safeguarded by having two doctors agreeing to do it. It was necessary for two doctors to sign a cremation form, but this did not stop Dr Harold Shipman from murdering more than 250 of his heartsink patients and then covering up his crime by having the body burnt.

It puts unfair pressure on the old and sick. Old people may feel that their lives are useless and opt for a pill to end it all simply because they are lonely.

It assumes that doctors know when patients are about to die. This is plain arrogance. Predicting death is like the weather forecast; you can be fairly accurate about today's outlook, less so about tomorrow's and after that it's largely guesswork.

It takes no account of medical discoveries. I have been continually surprised by medical advances that have turned terminal ilnesses into treatable conditions. A good example would be the treatment of pulmonary hypertension in babies. Previously it was rapidly fatal. Now we know it responds to Viagra. Who'd have thunk it?

It puts intolerable temptation in the hands of relatives. I have never been asked by a patient if I would kill her/him. But relatives have asked me to put gran out of her misery. With many having to sell the family house in order to pay nursing home fees, it doesn't take much to persuade a frail old lady that she would be doing everybody a favor by popping her clogs.

It devalues human life and dignity. I wouldn't allow a dog to suffer like that. You hear it said all the time. But a human being is not a dog. All human lives mean more than that. Just as the real response to an unwanted pregnancy should be care and support for the mother, so the correct response to the old and the dying should be care and support. Everybody has to die. But nobody should die alone, in pain and in sorrow. Shame on us that some should do so.

It smacks to me as a cost saving measure by a government strapped for cash. A famous "Yes Minister" TV program had the civil servants insisting that the most efficient hospital was one that didn't open to patients who would undoubtedly spoil the place. It may be a cheap way out to bump off these difficult patients, but that rather misses the point about what doctors are for.

I guess I could think of more reasons, but that should do.

Maverick

All my life I have been regarded as a maverick. I prefer to say I have an independent mind. The term comes from Samuel A Maverick, a Texan cattle raiser, who did not bother to brand his cattle. Thus he could claim that all unbranded cattle belonged to him. Later on it was applied to politics; someone who was unbranded, who did not acknowledge any party leadership.

It's probably fair to categorise me like this, because I like to think things out for myself rather than rely on other people's opinions. When I was first appointed as a hematologist I refused to be confined to the laboratory but went about actively treating patients others thought untreatable. I took on diseases that the internal medicine specialists didn't understand like SLE and scleroderma. I thought the hematology textbooks of the day were full on nonsense. I started reporting what I saw rather than what the textbook told me I ought to be seeing.

Then I turned myself into a medical oncologist. I had trained as a hematologist and as an immunologist, but it became apparent the principles used to treat leukemias and lymphomas could be applied to solid tumors like breast and bowel cancers. At the time the only people claiming to be oncologists outside major cancer centers were radiotherapists. When surgeons began to refer patients with solid tumors to me rather than them they began to resent it and called me a cowboy oncologist. Rather childishly I responded by devising a regimen for bladder cancer that I named "Blazing Saddles".

I raise this subject because of something I picked up from a televison program. I don't know whether Inspector Frost is required watching in many households, but I am a sucker for TV detectives. Frost is an awkward customer who can't fit in with what his bosses want. His superintendant warns him, "It's alright being a maverick, Frost, as long as you keep coming up with the goods; but one failure and you're vulnerable"

Later Frost accepts an apology from his subordinate. " We can't have out of order, son, but out of step - that's another thing. If you're out of step you step on things that other people miss.."

New wine

See how the sick need a doctor!
The children are dying for bread;
The Devil delights in his bombs and hatred
As panic and terror are spread.
The Church still debates its tradition,
Recalling the days that are dead,
When into the tumult there strides the Bridegroom
Demanding His Bride to be wed.

The trumpet sounds;
Listen to the shout!
Heaven opens wide;
Hear the angels sing!
All shall rise!
It’s the voice of victory
Raise your lamps to light
The coming King!


See how the world needs a Saviour!
The children are shrivelled and bored;
And mothers despair for their sons and daughters
As claims of the Christ are ignored.
But these are the days of new wineskins;
We watch as new wine is outpoured,
And see in the stretching out hands of Jesus
The joy of the world is restored.

The trumpet sounds;
Listen to the shout!
Heaven opens wide;
Hear the angels sing!
All shall rise!
It’s the voice of victory
Raise your lamps to light
The coming King

Bible reading

We had an interesting discussion on how to study the Bible tonight. Some people feel guilty if they don't read a chapter a day. Others swear by Bible Reading Notes. Some follow a system devised by CH Spurgeon, Alan Stibbs or IVP. I find the best way is to have to preach on a passage.

One thing I have tried is to write a hymn around a section of scripture. Those readers who liked my hymn "A precious people" might care to know that it comes from Colossians chapter 3 verses 12-17.