Tuesday, December 30, 2008
Images from Gaza
Someone has just sent me images from Gaza. Who could fail to be moved by a bleeding child. How callous and horrible must be the people who fire rockets on a foreign town while using children as a human shield just for the propaganda value of a bleeding child. No wonder the Geneva convention calls using civilians in this way a war crime.
Monday, December 29, 2008
Change! Change! Change! Mr Obama
Six bishops in the Church of England have now criticized the government over their being wedded to continuous economic growth. Gordon Brown wants us to start borrowing again. He wants the banks to offer easy credit once more.
As someone who is relatively rich I find it hard to criticize those poor people who want more, but I have to ask the question, "How much is enough?"
Through my letter box today came a magazine offering me such goodies as a telescope that will magnify 60 times for £60. Why would I want one? How about an official Swiss Military chrongraph for £300. It looks awfully like a wrist watch and I have one of those already. How about a car hammock for £25 or a slobber-free 'fetch' toy for dogs at only £9 or a giant electric lint shaver for £15? An instant stick-on shirt button? A solar marker light for paths and drives? Spykee - the first ever wi-fi robot, a snip at £279.95? Rechargeable color-changing flame lights? A natural woven willow hideaway for a wheelie bin?
Is this what is needed to keep the economy running? I sat down this morning wondering whether I should replace my VHS collection with DVDs. Yet I see in this magazine the offer of an old fashioned radiogram so I can play my old 45s or 33s. On my hard-drive recorder I have so many films and TV programmes recorded that I shall never have enough time to watch them. I started watching one tonight - Funny Face with Audry Hepburn and Fred Astair. I've never seen such tosh.
Our society has taken a wrong path. Perhaps bread and circuses are necessary to keep the peasants under control, but if so, what a mess we have made of our lives. Are there no real problems to solve in this world?
Israel declares total war on Hamas. I can see how they have been provoked, but is it likely to solve anything? People have selective memories. A man on talk radio was cursing the Israelis this morning. He complained that Palestinian territory had been annexed in 1967, as if there were no reason for it. As if the six-day war had never taken place.
He was probably too young to remember it - it was 41 years ago. He talked of the Palestinians as if they were not Arabs. Such ignorance! Here was someone who had not been subject to 60 years of brainwashing against Israel. What hope is there for a resolution.
The Old Testament solution would be to wipe out every last Hamas supporter; man woman and child. King Saul was punished even for sparing the King. I doubt that genocide would escape the notice of the world's press, and even George W Bush would be upset with them.
On the other hand, what can the Israelis do when hundreds of rockets rain down on their southern towns? Why do Hamas do it? They inflict very little damage on Israel. Is it to provoke a reaction like this? Do they hope to win a propaganda war? Do they think that Israel cares what the Europeans or the Russians or the Arabs think? Do they imagine America will abandon Israel when a large proportion of the American electorate believes that the return of the Jews to Jerusalem is one of the signs that presage the Second Coming?
Hamas won an election by promising to end corruption, to introduce good schools and a decent free health service. Wouldn't we all vote for motherhood and apple pie. They also promised to wipe Israel from the face of the earth. You probably wouldn't vote for a party that offered free health care, free education, and lower taxes. Your little grey cells would murmur, "It can't be done."
The West Bank and Gaza always was a failed state relying on hand-outs form a guilt-ridden Europe and America who together brought about the state of Israel, in part because of guilt about the Holocaust, in part to assuage Jewish voters and in part because of promises made by our grandfathers. This aid was only forthcoming if two mutually incompatible concepts could be believed at the same time: a free and secure Israel and a peaceful Palestinian homeland. Hamas won't buy into the former so the aid dried up.
The rockets are deliberately fired from densely populated areas. Hamas intends for civilians to be killed. How else can they mobilize the Western Press? Israel doesn't care. They know the Press will hammer them and they don't care. They might care if Obama withdrew American aid, but I bet he won't.
Result: stalemate. The war will continue - cold or hot.
Zadie Smith, the novelist, was guest editor on Radio 4 today. She sent a reporter to Liberia. Remember Liberia? That refuge for freed slaves from America? They elected a female President promising to end corruption. A renewed aid program began with her election. Hasn't it made a difference! Actually no. The aid has flowed into the hands of corrupt rulers; the poor have nothing.
Want to make a difference in this world? Plant a tree; write a book; father a child.
Now what's on television tonight?
As someone who is relatively rich I find it hard to criticize those poor people who want more, but I have to ask the question, "How much is enough?"
Through my letter box today came a magazine offering me such goodies as a telescope that will magnify 60 times for £60. Why would I want one? How about an official Swiss Military chrongraph for £300. It looks awfully like a wrist watch and I have one of those already. How about a car hammock for £25 or a slobber-free 'fetch' toy for dogs at only £9 or a giant electric lint shaver for £15? An instant stick-on shirt button? A solar marker light for paths and drives? Spykee - the first ever wi-fi robot, a snip at £279.95? Rechargeable color-changing flame lights? A natural woven willow hideaway for a wheelie bin?
Is this what is needed to keep the economy running? I sat down this morning wondering whether I should replace my VHS collection with DVDs. Yet I see in this magazine the offer of an old fashioned radiogram so I can play my old 45s or 33s. On my hard-drive recorder I have so many films and TV programmes recorded that I shall never have enough time to watch them. I started watching one tonight - Funny Face with Audry Hepburn and Fred Astair. I've never seen such tosh.
Our society has taken a wrong path. Perhaps bread and circuses are necessary to keep the peasants under control, but if so, what a mess we have made of our lives. Are there no real problems to solve in this world?
Israel declares total war on Hamas. I can see how they have been provoked, but is it likely to solve anything? People have selective memories. A man on talk radio was cursing the Israelis this morning. He complained that Palestinian territory had been annexed in 1967, as if there were no reason for it. As if the six-day war had never taken place.
He was probably too young to remember it - it was 41 years ago. He talked of the Palestinians as if they were not Arabs. Such ignorance! Here was someone who had not been subject to 60 years of brainwashing against Israel. What hope is there for a resolution.
The Old Testament solution would be to wipe out every last Hamas supporter; man woman and child. King Saul was punished even for sparing the King. I doubt that genocide would escape the notice of the world's press, and even George W Bush would be upset with them.
On the other hand, what can the Israelis do when hundreds of rockets rain down on their southern towns? Why do Hamas do it? They inflict very little damage on Israel. Is it to provoke a reaction like this? Do they hope to win a propaganda war? Do they think that Israel cares what the Europeans or the Russians or the Arabs think? Do they imagine America will abandon Israel when a large proportion of the American electorate believes that the return of the Jews to Jerusalem is one of the signs that presage the Second Coming?
Hamas won an election by promising to end corruption, to introduce good schools and a decent free health service. Wouldn't we all vote for motherhood and apple pie. They also promised to wipe Israel from the face of the earth. You probably wouldn't vote for a party that offered free health care, free education, and lower taxes. Your little grey cells would murmur, "It can't be done."
The West Bank and Gaza always was a failed state relying on hand-outs form a guilt-ridden Europe and America who together brought about the state of Israel, in part because of guilt about the Holocaust, in part to assuage Jewish voters and in part because of promises made by our grandfathers. This aid was only forthcoming if two mutually incompatible concepts could be believed at the same time: a free and secure Israel and a peaceful Palestinian homeland. Hamas won't buy into the former so the aid dried up.
The rockets are deliberately fired from densely populated areas. Hamas intends for civilians to be killed. How else can they mobilize the Western Press? Israel doesn't care. They know the Press will hammer them and they don't care. They might care if Obama withdrew American aid, but I bet he won't.
Result: stalemate. The war will continue - cold or hot.
Zadie Smith, the novelist, was guest editor on Radio 4 today. She sent a reporter to Liberia. Remember Liberia? That refuge for freed slaves from America? They elected a female President promising to end corruption. A renewed aid program began with her election. Hasn't it made a difference! Actually no. The aid has flowed into the hands of corrupt rulers; the poor have nothing.
Want to make a difference in this world? Plant a tree; write a book; father a child.
Now what's on television tonight?
Hsp90 again
Several people have asked about the status of heat shock protein 90, inhibition of which was thought of as a new way of treating the most aggressive forms of CLL. Unfortunately the two inhibitors that I described before have proved too toxic to the liver to hold out much hope for them to emerge as anti-CLL drugs. There were 32 papers at ASH which mentioned Hsp90, but most of them were irrelevant to CLL patients. Eloisi Caldas Lopes from Memorial Sloane Kettering described a new inhibitor, PUH-71, which is of a different chemical type to those previously described. This new agent was found to inhibit the growth of human diffuse large B-cell lymphomas in mice without liver toxicity. The agent was preferentially retained in the tumor tissue.
Other Hsp90 inhibitors are in the pipeline. Novartis have two, a pan-Histone deacetylase inhibitor, panobinostat, and a specific Hsp90 inhibitor, AUY, were both tested by Wang et al from MCG Cancer Center, Augusta, Georgia, in a system that stressed the mutant JAK2 status of myeloproliferative disease and both inhibited it through Hsp90 inhibition. In another study workers from Tokyo found that AUY when given with nilotinib could overcome the T315I mutant BCR-ABL that has so far produced a form of imatinib resistance in CML that could not otherwise be overcome. Panobinostat, meanwhile may act synergistically with bortezamib in mantle cell lymphoma (data from MCG Cancer Center, Augusta,H Lee Moffitt Cancer Center, Tampa, and Novartis Institute for Biomedical Research, Cambridge, MA. A phase II study of panobinostat in drug resistant myeloma is being carried out with some beneficial effects.
One of the other difficulties in Hsp90 inhibition is that it tends to upregulate Hsp72 which inhibits apoptosis. According to Emma Davenport and colleagues from the Insitute of Cancer Research, UK, this can be prevented by Hsp72 inhibitors such as KNK437 and triptolide.
John Byrd's group at Colombus, Ohio demonstrated that the Hsp90 inhibitor 17-DMAG represents a novel multi-targeted inhibitor of several critical kinases, transcription factors and anti-apoptosis genes relevant to CLL survival, and not just ZAP70, especially NF-kB. Given its oral formulation, which allows administration of 17-DMAG by continuous dosing and uninterrupted inhibition of Hsp90, initiation of phase II clinical trials in CLL that include detailed pharmacodynamic studies monitoring NF-kB target genes are indicated.
Jamie Cavenagh from Barts reported on a Phase I trial of KW-2478, a novel non-ansamycin, non-purine analogue antagonist for Hsp90. KW-2478 showed a potent anti-tumour activity both in vitro and in vivo in xenograft models, including activity in primary patient samples. The agent retained its activity in primary myeloma cells in the presence of BMSCs, suggesting that KW-2478 can overcome the protective effect of the bone marrow microenvironment. In the phase I trial there was no dose-limiting toxicity and the dose escalation continues.
From MDACC comes the small molecule WP1193, a caffeic acid derivative, which induced apoptosis in all types of drug-resistant CML cells. Treatment of the cells with WP1193 reduced levels of HSP90 transcripts, HSP90 protein and its client proteins, which include Bcr-Abl, Jak2 and Akt.
In conclusion, Hsp90 inhibition remains a promising treatment, not just for CLL, but for a range of different hematological tumors. Its effects are much more complicated that simply down-regulation of Zap-70, and care must be taken that a compensatory up-regulation of protective factors does not take place. The older geldanomycin derivatives may be too toxic for clinical use, but newer, perhaps less toxic inhibitors are in development.
Other Hsp90 inhibitors are in the pipeline. Novartis have two, a pan-Histone deacetylase inhibitor, panobinostat, and a specific Hsp90 inhibitor, AUY, were both tested by Wang et al from MCG Cancer Center, Augusta, Georgia, in a system that stressed the mutant JAK2 status of myeloproliferative disease and both inhibited it through Hsp90 inhibition. In another study workers from Tokyo found that AUY when given with nilotinib could overcome the T315I mutant BCR-ABL that has so far produced a form of imatinib resistance in CML that could not otherwise be overcome. Panobinostat, meanwhile may act synergistically with bortezamib in mantle cell lymphoma (data from MCG Cancer Center, Augusta,H Lee Moffitt Cancer Center, Tampa, and Novartis Institute for Biomedical Research, Cambridge, MA. A phase II study of panobinostat in drug resistant myeloma is being carried out with some beneficial effects.
One of the other difficulties in Hsp90 inhibition is that it tends to upregulate Hsp72 which inhibits apoptosis. According to Emma Davenport and colleagues from the Insitute of Cancer Research, UK, this can be prevented by Hsp72 inhibitors such as KNK437 and triptolide.
John Byrd's group at Colombus, Ohio demonstrated that the Hsp90 inhibitor 17-DMAG represents a novel multi-targeted inhibitor of several critical kinases, transcription factors and anti-apoptosis genes relevant to CLL survival, and not just ZAP70, especially NF-kB. Given its oral formulation, which allows administration of 17-DMAG by continuous dosing and uninterrupted inhibition of Hsp90, initiation of phase II clinical trials in CLL that include detailed pharmacodynamic studies monitoring NF-kB target genes are indicated.
Jamie Cavenagh from Barts reported on a Phase I trial of KW-2478, a novel non-ansamycin, non-purine analogue antagonist for Hsp90. KW-2478 showed a potent anti-tumour activity both in vitro and in vivo in xenograft models, including activity in primary patient samples. The agent retained its activity in primary myeloma cells in the presence of BMSCs, suggesting that KW-2478 can overcome the protective effect of the bone marrow microenvironment. In the phase I trial there was no dose-limiting toxicity and the dose escalation continues.
From MDACC comes the small molecule WP1193, a caffeic acid derivative, which induced apoptosis in all types of drug-resistant CML cells. Treatment of the cells with WP1193 reduced levels of HSP90 transcripts, HSP90 protein and its client proteins, which include Bcr-Abl, Jak2 and Akt.
In conclusion, Hsp90 inhibition remains a promising treatment, not just for CLL, but for a range of different hematological tumors. Its effects are much more complicated that simply down-regulation of Zap-70, and care must be taken that a compensatory up-regulation of protective factors does not take place. The older geldanomycin derivatives may be too toxic for clinical use, but newer, perhaps less toxic inhibitors are in development.
Sunday, December 28, 2008
The platelets - preservatives within the blood.
When I was first converted I used to give a talk about the blood based on the text "The blood of Jesus Christ cleanses is from all unrighteousness".
Considering the mess it makes when it is spilled it is hard to think of blood as a cleansing agent. But, of course, the white blood cells are just that. Without them we become infected with the foulest infections but they are there in the blood to seek out every bacterium wherever it is in the body. No nook or cranny exists but a white cell finds a way in and eats the germ.
That's not all blood does. Red cells carry life-giving oxygen. Watch an anemic patient who is given a blood transfusion. Where they were weak and listless, hardly able to raise themselves from their bed, they become invigorated, vibrant and energetic. "The life is in the blood" says the Bible and you can see what it means. The blood of Jesus Christ not only cleanses, it brings new life.
But apart from red cells and white cells there is a third type of cell that is not much spoken of - the platelet. What does a platelet do? It rushes to fill in holes so the blood doesn't seep out. And that is my topic today. What is it that prevents our faith from seeping away?
I Peter 1:4-5 talks about our inheritance that can never perish, spoil or fade - kept in heaven for us, who through faith are shielded by God's power until the salvation that is ready to be revealed at the last time.
The doctrine of the final perseverance of the saints (or preservation if you prefer) is the final 'P' in TULIP, one of the five points of Calvinism that many people abhor. The doctrine is logical; it seeks to give glory to God for everything. We are saved through God's intervention - we cannot save ourselves because we are Totally depraved - not that we are extremely horrible in every part, but that every part of us has been touched by the corruption of sin; even our wills so that we cannot choose for ourselves to believe God whose Unconditional election instead chooses us - He chooses us not because we have any merit, but because He loves us. Our salvation was achieved on the cross, but the atonement although available to all who would choose to be saved is Limited to the elect because only those who are chosen by God are able to choose Him. It is all of grace and none of works, but this grace is Irresistible - despite our sinful hearts we cannot resist Him, and since it is He who saves to the uttermost it is He who Preserves for eternal life would not be eternal if it had an end.
Nevertheless, TULIP does not carry universal approval, for some will say that it is a man-made concoction produced by selecting certain texts and ignoring contradicting ones, and in any case it does not concur with our experience, for it is clear that some do fall away.
So, there are some who doubt the final preservation of the saints, but there are some that distort it. It is not true that one conversion experience in a great tent somewhere sets you up for life. Alec Motyer tells of the time when he, as a curate in London, was given the task of following up those who had 'gone forward' at the Billy Graham Haringey Crusade. It was a soul destroying experience, he said, for every door he knocked at was either closed to him or greeted him with an embarrassed confession that yes, he had gone forward, but it was a thing of the moment. We all know of people who seemed wonderfully saved, but six weeks later were living their lives in exactly the same way they always had.
Jesus in the parable of the sower, tells is that are many kinds of soil on which the seed falls, and although it may spring up, if it has no roots it will wither and die. In Mark 13:13 it is he who stands firm to the end who will be saved. Salvation is not for those who 'make a decision' but for those who repent; those who think again; those who change their way of thinking, not just change their mind to have it changed back again next week.
We need to be a Gospel people, who always keep the cross before us. Some think the Gospel old hat; an old story that needs to be told to children, but when we are mature please explain to us exactly what Leviticus is about; help us to understand Ezekiel; reveal to us what Revelation means; dare to take us through the second half of Daniel. If we don't continue to keep the Gospel before us we will grow cold in our faith, not recognising the love of God.
Don't assume that the 'old man' within you is dead; he is only sleeping. We need to be a people of repentance. Backsliding follows for those who think they don't need to repent. "Give us this day our daily bread" is followed immediately by "Forgive us our trespasses". There is no such thing as sinless perfection this side of the grave.
Jesus' followers were called disciples because they were under discipline, and we, too, must discipline ourselves if we are to follow him. Prayer, bible reading, and the fellowship of other believers all preserve us - they are the means of grace employed by the Holy Spirit.
I know my faults only too well and perseverance isn't one of them. I am easily distracted. I have one of those wood pigeon minds that pecks a bit here, then there, then over the fence in someone else's garden. I would never eat my way through a whole field of wheat - I'd be too attracted by the barley across the way. I think I have four books on the go at the minute and I'm following about seven TV series. How could I be expected to persevere? Only in God's strength. Ephesians 6:10 tells us to be strong in the Lord and in His mighty power. That is the only way it is possible. You see, we are shielded by God's mighty power.
If it doesn't seem true - you've seen too many fall away - then consider whether they were truly saved, and if you think they were then consider whether they are just backsliding and one day will return. Martin Lloyd Jones tells of a man who seemed to have made a shipwreck of his faith and was so distressed that he was on his way to jump off London Bridge. As he passed by Westminster Chapel he remembered that he had promised himself that he would hear MLJ preach one time before he died. He went in, but was barred from the sanctuary because MLJ was praying. He heard his prayer - "We pray for those here who are backsliding". That day he was wonderfully restored to faith. If your friends or relatives seem to have fallen away then pray for them. Even if you do not see them restored in this life, even if they show no evidence of it, who are you to make that judgement? Thank God only God is required to judge one man from another. Shall not the judge of all the earth do right?
What about those texts that suggest that the saved may yet be lost? We must read every text in context but this is an eternal promise: "All that the Father gives me will come to me, and whoever comes to me I will never drive away. For I have come down from heaven not to do my will but to do the will of him who sent me. And this is the will of him who sent me, that I shall lose none of all that he has given me, but raise them up at the last day. For my Father's will is that everyone who looks to the Son and believes in him shall have eternal life, and I will raise him up at the last day."
It is because we have the shield of God's power that we are safe. When you put your hand in the hand of the one who holds the Universe in place, He won't let you go no matter how slippery you are.
Considering the mess it makes when it is spilled it is hard to think of blood as a cleansing agent. But, of course, the white blood cells are just that. Without them we become infected with the foulest infections but they are there in the blood to seek out every bacterium wherever it is in the body. No nook or cranny exists but a white cell finds a way in and eats the germ.
That's not all blood does. Red cells carry life-giving oxygen. Watch an anemic patient who is given a blood transfusion. Where they were weak and listless, hardly able to raise themselves from their bed, they become invigorated, vibrant and energetic. "The life is in the blood" says the Bible and you can see what it means. The blood of Jesus Christ not only cleanses, it brings new life.
But apart from red cells and white cells there is a third type of cell that is not much spoken of - the platelet. What does a platelet do? It rushes to fill in holes so the blood doesn't seep out. And that is my topic today. What is it that prevents our faith from seeping away?
I Peter 1:4-5 talks about our inheritance that can never perish, spoil or fade - kept in heaven for us, who through faith are shielded by God's power until the salvation that is ready to be revealed at the last time.
The doctrine of the final perseverance of the saints (or preservation if you prefer) is the final 'P' in TULIP, one of the five points of Calvinism that many people abhor. The doctrine is logical; it seeks to give glory to God for everything. We are saved through God's intervention - we cannot save ourselves because we are Totally depraved - not that we are extremely horrible in every part, but that every part of us has been touched by the corruption of sin; even our wills so that we cannot choose for ourselves to believe God whose Unconditional election instead chooses us - He chooses us not because we have any merit, but because He loves us. Our salvation was achieved on the cross, but the atonement although available to all who would choose to be saved is Limited to the elect because only those who are chosen by God are able to choose Him. It is all of grace and none of works, but this grace is Irresistible - despite our sinful hearts we cannot resist Him, and since it is He who saves to the uttermost it is He who Preserves for eternal life would not be eternal if it had an end.
Nevertheless, TULIP does not carry universal approval, for some will say that it is a man-made concoction produced by selecting certain texts and ignoring contradicting ones, and in any case it does not concur with our experience, for it is clear that some do fall away.
So, there are some who doubt the final preservation of the saints, but there are some that distort it. It is not true that one conversion experience in a great tent somewhere sets you up for life. Alec Motyer tells of the time when he, as a curate in London, was given the task of following up those who had 'gone forward' at the Billy Graham Haringey Crusade. It was a soul destroying experience, he said, for every door he knocked at was either closed to him or greeted him with an embarrassed confession that yes, he had gone forward, but it was a thing of the moment. We all know of people who seemed wonderfully saved, but six weeks later were living their lives in exactly the same way they always had.
Jesus in the parable of the sower, tells is that are many kinds of soil on which the seed falls, and although it may spring up, if it has no roots it will wither and die. In Mark 13:13 it is he who stands firm to the end who will be saved. Salvation is not for those who 'make a decision' but for those who repent; those who think again; those who change their way of thinking, not just change their mind to have it changed back again next week.
We need to be a Gospel people, who always keep the cross before us. Some think the Gospel old hat; an old story that needs to be told to children, but when we are mature please explain to us exactly what Leviticus is about; help us to understand Ezekiel; reveal to us what Revelation means; dare to take us through the second half of Daniel. If we don't continue to keep the Gospel before us we will grow cold in our faith, not recognising the love of God.
Don't assume that the 'old man' within you is dead; he is only sleeping. We need to be a people of repentance. Backsliding follows for those who think they don't need to repent. "Give us this day our daily bread" is followed immediately by "Forgive us our trespasses". There is no such thing as sinless perfection this side of the grave.
Jesus' followers were called disciples because they were under discipline, and we, too, must discipline ourselves if we are to follow him. Prayer, bible reading, and the fellowship of other believers all preserve us - they are the means of grace employed by the Holy Spirit.
I know my faults only too well and perseverance isn't one of them. I am easily distracted. I have one of those wood pigeon minds that pecks a bit here, then there, then over the fence in someone else's garden. I would never eat my way through a whole field of wheat - I'd be too attracted by the barley across the way. I think I have four books on the go at the minute and I'm following about seven TV series. How could I be expected to persevere? Only in God's strength. Ephesians 6:10 tells us to be strong in the Lord and in His mighty power. That is the only way it is possible. You see, we are shielded by God's mighty power.
If it doesn't seem true - you've seen too many fall away - then consider whether they were truly saved, and if you think they were then consider whether they are just backsliding and one day will return. Martin Lloyd Jones tells of a man who seemed to have made a shipwreck of his faith and was so distressed that he was on his way to jump off London Bridge. As he passed by Westminster Chapel he remembered that he had promised himself that he would hear MLJ preach one time before he died. He went in, but was barred from the sanctuary because MLJ was praying. He heard his prayer - "We pray for those here who are backsliding". That day he was wonderfully restored to faith. If your friends or relatives seem to have fallen away then pray for them. Even if you do not see them restored in this life, even if they show no evidence of it, who are you to make that judgement? Thank God only God is required to judge one man from another. Shall not the judge of all the earth do right?
What about those texts that suggest that the saved may yet be lost? We must read every text in context but this is an eternal promise: "All that the Father gives me will come to me, and whoever comes to me I will never drive away. For I have come down from heaven not to do my will but to do the will of him who sent me. And this is the will of him who sent me, that I shall lose none of all that he has given me, but raise them up at the last day. For my Father's will is that everyone who looks to the Son and believes in him shall have eternal life, and I will raise him up at the last day."
It is because we have the shield of God's power that we are safe. When you put your hand in the hand of the one who holds the Universe in place, He won't let you go no matter how slippery you are.
Thursday, December 25, 2008
Little Dorrit
Everyone knows that what the BBC does best is its period dramas. After last year’s phenomenally successful 'Bleak House' it has just broadcast a new version of 'Little Dorrit' broken up into half hourly episodes. There is an older version starring Alec Guinness which I found unwatchable, but this one is the real goods. It will be broadcast on PBS Masterpiece in the New Year - don't miss it!
The elderly Dorrit, Father of Marshalsea, is played by Tom Courtenay and his daughter Amy (Little Dorrit) by Claire Foy. Matthew Macfadyen plays Arthur Clennam wonderfully well, even if he is too young for the part. The grotesques are glorious. Judy Parfitt as Mrs Clennam, Alun Armstrong as Jeremiah Flintwinch, Sue Johnson as Affery, Amanda Redman as Mrs Merdle, Ruth Jones as Flora Finching, and especially Andy Serkis as Rigaud.
It is well known that Dickens’s own father was committed to a debtor’s prison and he is the model for the elderly Dorrit, just as he was for Mr Micawber in David Copperfield. Despite his fame as a popular novelist and his ability to construct memorable characters, Dickens was principally a satirist and his target in this novel was mainly the debtor’s prison – long since disappeared. Do not think that the satire ends there, there are secondary targets. Government bureaucracy in the form of the Circumlocution Office is wonderfully portrayed. You need to stand in a line waiting to receive a form that you must fill in to ask permission to fill in a second form requesting permission to make a request of the office. It is run by Tite Barnacle (brilliantly portrayed by 82-year old Robert Hardy) and his family, whose aim in life is to do nothing and whose time is spent discussing matters of no consequence so as to avoid doing any work – and all for a fat salary and gold plated pension. Twenty years ago ‘Yes Minister’ demonstrated that the Civil Service had not changed and news items this week see it similarly set in stone. Civil Servants are looking for ways to prevent having to put into action a ministerial decree that criminals doing ‘community service’ should wear fluorescent jackets identifying them as such.
Even more relevant was the avaricious affluent society as a target. Mr Merdle, the ‘man of the moment’ into whose bank all Society wished to invest could well have been Bernie Madoff – he was running a similar ‘Ponzi scheme’. Mrs Merdle is referred to in the novel as ‘the bosom’ on which Mr Merdle displayed his jewels. Amanda Redman plays ‘the bosom’ very well indeed. The bankruptcy of Mr Merdle may be seen as just a plot device to bring a reversal of fortune to Arthur Clennam, but Dickens makes it a comment on both his and our society. Here’s what he wrote, “Numbers of men in every profession and trade would be blighted by his insolvency; old people who had been in easy circumstances all their lives would have no place for their repentance for their trust in him but the workhouse; legions of women and children would have their whole future desolated by this mighty scoundrel.”
As we see the fallout of the Madoff swindle we see how perceptive was Dickens. Already one naïve investor has killed himself. In the book it is Merdle himself who commits suicide (typically with a borrowed penknife in a hot bath). But the Dickensian description elevates this tawdry act to something more: "a new constellation to be followed by the wise men bringing gifts until it stopped over a certain carrion at the bottom of a bath and disappeared".
These greedy men who make the acquisition of money their end are the Antichrist, he says.
The elderly Dorrit, Father of Marshalsea, is played by Tom Courtenay and his daughter Amy (Little Dorrit) by Claire Foy. Matthew Macfadyen plays Arthur Clennam wonderfully well, even if he is too young for the part. The grotesques are glorious. Judy Parfitt as Mrs Clennam, Alun Armstrong as Jeremiah Flintwinch, Sue Johnson as Affery, Amanda Redman as Mrs Merdle, Ruth Jones as Flora Finching, and especially Andy Serkis as Rigaud.
It is well known that Dickens’s own father was committed to a debtor’s prison and he is the model for the elderly Dorrit, just as he was for Mr Micawber in David Copperfield. Despite his fame as a popular novelist and his ability to construct memorable characters, Dickens was principally a satirist and his target in this novel was mainly the debtor’s prison – long since disappeared. Do not think that the satire ends there, there are secondary targets. Government bureaucracy in the form of the Circumlocution Office is wonderfully portrayed. You need to stand in a line waiting to receive a form that you must fill in to ask permission to fill in a second form requesting permission to make a request of the office. It is run by Tite Barnacle (brilliantly portrayed by 82-year old Robert Hardy) and his family, whose aim in life is to do nothing and whose time is spent discussing matters of no consequence so as to avoid doing any work – and all for a fat salary and gold plated pension. Twenty years ago ‘Yes Minister’ demonstrated that the Civil Service had not changed and news items this week see it similarly set in stone. Civil Servants are looking for ways to prevent having to put into action a ministerial decree that criminals doing ‘community service’ should wear fluorescent jackets identifying them as such.
Even more relevant was the avaricious affluent society as a target. Mr Merdle, the ‘man of the moment’ into whose bank all Society wished to invest could well have been Bernie Madoff – he was running a similar ‘Ponzi scheme’. Mrs Merdle is referred to in the novel as ‘the bosom’ on which Mr Merdle displayed his jewels. Amanda Redman plays ‘the bosom’ very well indeed. The bankruptcy of Mr Merdle may be seen as just a plot device to bring a reversal of fortune to Arthur Clennam, but Dickens makes it a comment on both his and our society. Here’s what he wrote, “Numbers of men in every profession and trade would be blighted by his insolvency; old people who had been in easy circumstances all their lives would have no place for their repentance for their trust in him but the workhouse; legions of women and children would have their whole future desolated by this mighty scoundrel.”
As we see the fallout of the Madoff swindle we see how perceptive was Dickens. Already one naïve investor has killed himself. In the book it is Merdle himself who commits suicide (typically with a borrowed penknife in a hot bath). But the Dickensian description elevates this tawdry act to something more: "a new constellation to be followed by the wise men bringing gifts until it stopped over a certain carrion at the bottom of a bath and disappeared".
These greedy men who make the acquisition of money their end are the Antichrist, he says.
Sunday, December 21, 2008
ASH 1 - The German CLL8 trial
For CLL patients and doctors alike, the main event at ASH was the German CLL8 trial comparing FC with FCR. We already knew from the Roche website that the trial had shown that FCR was sufficiently better than FC for the trial to be stopped after the first interim analysis, but this was our first opportunity to examine the details.
817 patients from several countries were randomized between FC and FCR in standard dosages. The patients were younger than most with a median age of 61 (though some patients were as old as 80) and they were fit with good kidney function. 61% were Binet stage B and 32% stage C, so it is unlikely that this trial took the easy way out by treating patients that didn't really need treating. The overall incidences of trisomy 12 and abnormalities of 13q, 11q23, and 17p13 detected by FISH were 12%, 57%, 25%, and 8%, respectively, with no statistically significant differences between treatment arms. On average patients managed to get 5 of the recommended 6 courses in.
Analysis was in June 2008, with a median of just over 2 years follow-up. Overall response rate was significantly higher for the FCR arm (95% v 88%; p=0.001). The CR rate (1996 NCI criteria) was significantly higher for the FCR arm (52% v 27%; p<0.0001). Progression-free survival was was 76.6% at 2 years in the FCR arm and 62.3% in the FC arm (p<0.0001). But the difference for overall survival was not significant (91% v 88% at 2 years).
Adding the rituximab resulted in more toxicity. Grade 3 and 4 events occurred in 62% v 47% and severe hematologic toxicity in 55% v 39% (the significant difference was for neutropenia), but there was no significant difference in the incidence of serious infections (18.8% v 14.8%) nor of treatment related mortality (2% v 1.5%).
Minimal residual disease (MRD) was assessed in this trial in both blood and bone marrow by 4-color flow - capable of detecting one residual cell among 10,000 tested (for comparison a CR just means that there are fewer than 30% lymphocytes in the bone marrow). Assessment was after 3 courses of treatment, again one month after finishing treatment and again three months after treatment. Whether tested on blood or bone marrow and at whatever time tested there was significantly less residual disease in the FCR arm than in the FC arm. For example, fewer than one in 10,000 cells were detected in 33.6% vs. 6.4% at the first assessment of blood MRD, 67.6% vs. 36.6% at the second and 66.4% vs. 34.2% at the final assessment (for all comparisons FCR is first and p < 0.0001). The results from the marrow showed slightly less clearance of MRD (eg 47.6% v 66.4% for the final assessment of the FCR arm).
Progression-free survival (PFS) was greater if lower levels of MRD were achieved. Although this was more likely when rituximab was included, if it could be achieved it didn't matter which arm of the trial was involved. If FC can give fewer than 1 cell in 10,000 at the final assessment, progression-free survival will be no longer if rituximab is added.
Incidentally, this trial compared two methods of detecting MRD, the 4 color flow method described above and an RQ-PCR method. The results were virtually identical where more than 1 in 10,000 cells were detectable, but below that level RQ-PCR was more sensitive.
Any residual cells present up to 180 days after the last rituximab infusion lacked CD20 - evidence that persisting antibody continued to modulate the antigen.
The trial also looked at the role of prognostic markers in this trial. The incidences of the most common genomic aberrations were 13q- 56.7%, 13q- single 36.4%, 11q- 24.6%, +12 12.0%, and 17p- 8.2%. IGHV was unmutated in 63.4% and V3-21 was rearranged in 4.9%. AS expected, particularly poor outcomes were observed for 17p- in both arms (FC and FCR): CR (4.5% and 19.0%), CR+PR (45.5% and 71.4%), PFS (at 24 months: 0.0% and 29.6%), and OS (at 24 months: 41.0% and 53.3%). However, even these poor results do not suggest that rituximab is completely inactive in p53 deleted disease. Unmutated IGHV gene status was associated with shorter PFS in both arms combined and individually (all p<.001), shorter overall survival in the FC arm (p=.006), and probably in the FCR arm though follow-up is not long enough for this to be statistically significant (p=.092).
Multivariate analysis was applied to the trial. Regarding PFS, independent prognostic factors were 17p- (Hazard Ratio (HR) 6.76, p<.001), unmutated IGHV(HR 1.97, p<.001), FCR (HR 0.51, p<.001) and +12 (HR 0.58, p=.020). Regarding overall survival, only 17p- (HR 7.47, p<.001) and unmutated IGHV (HR 2.09, p=.018) were identified as significant independent factors, though FCR might be with longer follow-up (HR 0.66, p=.085).
In conclusion, genetic parameters remain powerful prognostic markers after 1st line FC and FCR treatment. The overall improvements by FCR result from specific treatment effects in distinct genetic subgroups. It seems particularly important that patients with 11q- appears to benefit most from the addition of rituximab. However, 17p- and unmutated IGHV status remain predictors for shorter PFS and OS independently of the overall improvement by FCR.
817 patients from several countries were randomized between FC and FCR in standard dosages. The patients were younger than most with a median age of 61 (though some patients were as old as 80) and they were fit with good kidney function. 61% were Binet stage B and 32% stage C, so it is unlikely that this trial took the easy way out by treating patients that didn't really need treating. The overall incidences of trisomy 12 and abnormalities of 13q, 11q23, and 17p13 detected by FISH were 12%, 57%, 25%, and 8%, respectively, with no statistically significant differences between treatment arms. On average patients managed to get 5 of the recommended 6 courses in.
Analysis was in June 2008, with a median of just over 2 years follow-up. Overall response rate was significantly higher for the FCR arm (95% v 88%; p=0.001). The CR rate (1996 NCI criteria) was significantly higher for the FCR arm (52% v 27%; p<0.0001). Progression-free survival was was 76.6% at 2 years in the FCR arm and 62.3% in the FC arm (p<0.0001). But the difference for overall survival was not significant (91% v 88% at 2 years).
Adding the rituximab resulted in more toxicity. Grade 3 and 4 events occurred in 62% v 47% and severe hematologic toxicity in 55% v 39% (the significant difference was for neutropenia), but there was no significant difference in the incidence of serious infections (18.8% v 14.8%) nor of treatment related mortality (2% v 1.5%).
Minimal residual disease (MRD) was assessed in this trial in both blood and bone marrow by 4-color flow - capable of detecting one residual cell among 10,000 tested (for comparison a CR just means that there are fewer than 30% lymphocytes in the bone marrow). Assessment was after 3 courses of treatment, again one month after finishing treatment and again three months after treatment. Whether tested on blood or bone marrow and at whatever time tested there was significantly less residual disease in the FCR arm than in the FC arm. For example, fewer than one in 10,000 cells were detected in 33.6% vs. 6.4% at the first assessment of blood MRD, 67.6% vs. 36.6% at the second and 66.4% vs. 34.2% at the final assessment (for all comparisons FCR is first and p < 0.0001). The results from the marrow showed slightly less clearance of MRD (eg 47.6% v 66.4% for the final assessment of the FCR arm).
Progression-free survival (PFS) was greater if lower levels of MRD were achieved. Although this was more likely when rituximab was included, if it could be achieved it didn't matter which arm of the trial was involved. If FC can give fewer than 1 cell in 10,000 at the final assessment, progression-free survival will be no longer if rituximab is added.
Incidentally, this trial compared two methods of detecting MRD, the 4 color flow method described above and an RQ-PCR method. The results were virtually identical where more than 1 in 10,000 cells were detectable, but below that level RQ-PCR was more sensitive.
Any residual cells present up to 180 days after the last rituximab infusion lacked CD20 - evidence that persisting antibody continued to modulate the antigen.
The trial also looked at the role of prognostic markers in this trial. The incidences of the most common genomic aberrations were 13q- 56.7%, 13q- single 36.4%, 11q- 24.6%, +12 12.0%, and 17p- 8.2%. IGHV was unmutated in 63.4% and V3-21 was rearranged in 4.9%. AS expected, particularly poor outcomes were observed for 17p- in both arms (FC and FCR): CR (4.5% and 19.0%), CR+PR (45.5% and 71.4%), PFS (at 24 months: 0.0% and 29.6%), and OS (at 24 months: 41.0% and 53.3%). However, even these poor results do not suggest that rituximab is completely inactive in p53 deleted disease. Unmutated IGHV gene status was associated with shorter PFS in both arms combined and individually (all p<.001), shorter overall survival in the FC arm (p=.006), and probably in the FCR arm though follow-up is not long enough for this to be statistically significant (p=.092).
Multivariate analysis was applied to the trial. Regarding PFS, independent prognostic factors were 17p- (Hazard Ratio (HR) 6.76, p<.001), unmutated IGHV(HR 1.97, p<.001), FCR (HR 0.51, p<.001) and +12 (HR 0.58, p=.020). Regarding overall survival, only 17p- (HR 7.47, p<.001) and unmutated IGHV (HR 2.09, p=.018) were identified as significant independent factors, though FCR might be with longer follow-up (HR 0.66, p=.085).
In conclusion, genetic parameters remain powerful prognostic markers after 1st line FC and FCR treatment. The overall improvements by FCR result from specific treatment effects in distinct genetic subgroups. It seems particularly important that patients with 11q- appears to benefit most from the addition of rituximab. However, 17p- and unmutated IGHV status remain predictors for shorter PFS and OS independently of the overall improvement by FCR.
No blogging
I have not been blogging much recently. I had the beginnings of a virus in San Francisco and this developed into a heavy cold - what most people have been calling 'flu, but certainly isn't. I have had 'flu three times in my life and it is a much worse illness than this. A severe headache, a high fever, pains in the joints, shivering attacks and a complete listlessness; it is completely impossible to get out of bed. This has been characterized by tiredness, joint pains, sneezing, a sore throat and more recently a stuffy nose and a tickly cough. However, I have certainly not felt like working and have spent my time doing SUDOKU puzzles and watching old episodes of Poirot.
What I am beginning to do is to write my impressions of ASH which I will next blog about.
What I am beginning to do is to write my impressions of ASH which I will next blog about.
Wednesday, December 17, 2008
Judgement at Nuremberg
I was 18 when Judgement at Nuremberg was released, but I first watched it a couple of nights ago. It is a serious film about the second world war. For my generation this was the greatest event in our lives. It casts its shadow over the whole of the twentieth century. Just think of what it signified: the wholesale slaughter of six million Jews, the dawn of the nuclear age, aerial bombing on a vast scale, the subjection of millions to communism, the emergence of America as the greatest power the world has ever seen, the jet engine, rockets, penicillin, the emergence of democracy in Japan, the end of the British and French Empires, the discrediting of Eugenics.
The film is a major production that was nominated for 12 Oscars and awarded two. It starred Spencer Tracy, Burt Lancaster, Richard Widmark, Marlene Dietrich, Maximillian Schell, Montgomery Clift, Judy Garland and even a very young William Shattner. It explores the question of human responsibility. It is a very Calvinist film.
Briefly, a retired circuit judge (Tracy) from Maine is called on to chair a tribunal examining the responsibility of German Judges for the implementation of Nazi laws that required the sterilization and later the extermination of Jews, the mentally handicapped and other 'socially undesirables'. Burt Lancaster plays the chief defendant, a senior and respected German jurist who helped frame the Wiemar Constitution and had written many books on jurisprudence. His role has very few lines apart from one central and long speech accepting culpability. Richard Widmark is the prosecuting counsel, and American army colonel who led the group that first entered Dachau. He is wild eyed and determined for revenge. He likes to show the film of what was discovered at Dachau and by British troops at Belsen at every trial. Maximillian Schell plays a German advocate who is defending counsel. Darkly handsome with a winning smile, he was a wise choice for the Oscar that year. He seeks to exculpate the judges by declaring that they were simply being patriotic; upholding the laws of their country. They had no responsibility for framing the laws, but had to do their duty in enforcing them. His shock of black hair means that he has some resemblance to Adolf Hitler, and he adopts some of Hitler's verbal tricks, so that as you feels yourself warming to him you also begin to realise how so many Germans fell for Hitler.
In order to justify the judges actions he is forced to re-examine two old cases. The first concerns the forced sterilisation of a common laborer for familial mental retardation. Montgomery Clift plays the part of the victim. Although he conveys the anguish of his situation, he is unbelievable as a half-wit. As a result we see it as an injustice as an ordinary working man is sterilised, but had he appeared less intelligent would he not have got the audience asking - well, perhaps he should be sterilized? For Schell demonstrates that the idea of Eugenics was not a German one. He could well have quoted from Francis Galton, but in fact goes to Oliver Wendall Holmes and the Virginian Constitutional amendments. I still hear people bemoaning the fact that the intelligentsia have too few babies and the less clever working class too many.
The second case involved a young Aryan girl who had supposedly been seduced by an old Jew, who had been executed for his crime. The girl was played by Judy Garland in a performance that finally unstrung her from the rainbow. Schell harries her to admit that she really was the old Jews mistress, but she continues to deny it - he was an old family friend. Strictly speaking Garland is too old for the role, but it is still a great performance and it is her anguish that prompts the Burt Lancaster character to make a statement that admits his guilt.
The film is set in 1948, the year that Czechoslovakia was taken over by the communists and the year of the Berlin airlift. The Americans were under pressure to establish West Germany as a friendly power and a bulwark against communism. Pressure is put on the old judge to be nice to the Germans - as a senior officer puts it the call of patriotism is more important than legal niceties. But this is exactly what the trial is about, what the film is about and why it is so relevant for today.
Some sections of society ask our judges to be merciful. That is wrong. Our judges must first and foremost be just. Convicting the guilty is as important as clearing the innocent. In the IG Farber case, running at the same time, the defendants were sometimes acquitted but even is convicted received token sentences.
The judge convicts the judges and hands out life sentences. Sentencing is part of the verdict. A token sentence says you are guilty but not very. There is a place for mercy, but that is in the hands of the Sovereign. Only he or she can dispense it.
Schell seeks to lessen the crime of the judges by saying we are all guilty. The Vatican in signing the Concordat in 1933, the Russians in signing the non-aggression pact, the American industrialists who traded with Germany, those who stood by as Germany invaded the Saar, Austria and the Sudetenland, and even Winston Churchill who wrote to the Times saying that in order to resist the German aggression, Britain needed a leader with the determination and leadership qualities of an Adolf Hitler.
As the Spencer Tracy character seeks to understand the German people he talks to servants and aristocrats, all of whom knew nothing of what was happening in the 'camps'. He doesn't believe a word of it. He accepts that there is a measure of guilt everywhere, but that doesn't lessen the guilt of the judges.
In a final confrontation with the Burt Lancaster character, the convicted judge pleads that he did not realise how it would end up, with so many millions dying. Tracy replies that it ended up like this the moment you sent an innocent man for execution.
Calvinist? Because it insists that everyone is guilty, and each is responsible for his own guilt. The pass mark is not lowered just because the standard is so low.
The film is a major production that was nominated for 12 Oscars and awarded two. It starred Spencer Tracy, Burt Lancaster, Richard Widmark, Marlene Dietrich, Maximillian Schell, Montgomery Clift, Judy Garland and even a very young William Shattner. It explores the question of human responsibility. It is a very Calvinist film.
Briefly, a retired circuit judge (Tracy) from Maine is called on to chair a tribunal examining the responsibility of German Judges for the implementation of Nazi laws that required the sterilization and later the extermination of Jews, the mentally handicapped and other 'socially undesirables'. Burt Lancaster plays the chief defendant, a senior and respected German jurist who helped frame the Wiemar Constitution and had written many books on jurisprudence. His role has very few lines apart from one central and long speech accepting culpability. Richard Widmark is the prosecuting counsel, and American army colonel who led the group that first entered Dachau. He is wild eyed and determined for revenge. He likes to show the film of what was discovered at Dachau and by British troops at Belsen at every trial. Maximillian Schell plays a German advocate who is defending counsel. Darkly handsome with a winning smile, he was a wise choice for the Oscar that year. He seeks to exculpate the judges by declaring that they were simply being patriotic; upholding the laws of their country. They had no responsibility for framing the laws, but had to do their duty in enforcing them. His shock of black hair means that he has some resemblance to Adolf Hitler, and he adopts some of Hitler's verbal tricks, so that as you feels yourself warming to him you also begin to realise how so many Germans fell for Hitler.
In order to justify the judges actions he is forced to re-examine two old cases. The first concerns the forced sterilisation of a common laborer for familial mental retardation. Montgomery Clift plays the part of the victim. Although he conveys the anguish of his situation, he is unbelievable as a half-wit. As a result we see it as an injustice as an ordinary working man is sterilised, but had he appeared less intelligent would he not have got the audience asking - well, perhaps he should be sterilized? For Schell demonstrates that the idea of Eugenics was not a German one. He could well have quoted from Francis Galton, but in fact goes to Oliver Wendall Holmes and the Virginian Constitutional amendments. I still hear people bemoaning the fact that the intelligentsia have too few babies and the less clever working class too many.
The second case involved a young Aryan girl who had supposedly been seduced by an old Jew, who had been executed for his crime. The girl was played by Judy Garland in a performance that finally unstrung her from the rainbow. Schell harries her to admit that she really was the old Jews mistress, but she continues to deny it - he was an old family friend. Strictly speaking Garland is too old for the role, but it is still a great performance and it is her anguish that prompts the Burt Lancaster character to make a statement that admits his guilt.
The film is set in 1948, the year that Czechoslovakia was taken over by the communists and the year of the Berlin airlift. The Americans were under pressure to establish West Germany as a friendly power and a bulwark against communism. Pressure is put on the old judge to be nice to the Germans - as a senior officer puts it the call of patriotism is more important than legal niceties. But this is exactly what the trial is about, what the film is about and why it is so relevant for today.
Some sections of society ask our judges to be merciful. That is wrong. Our judges must first and foremost be just. Convicting the guilty is as important as clearing the innocent. In the IG Farber case, running at the same time, the defendants were sometimes acquitted but even is convicted received token sentences.
The judge convicts the judges and hands out life sentences. Sentencing is part of the verdict. A token sentence says you are guilty but not very. There is a place for mercy, but that is in the hands of the Sovereign. Only he or she can dispense it.
Schell seeks to lessen the crime of the judges by saying we are all guilty. The Vatican in signing the Concordat in 1933, the Russians in signing the non-aggression pact, the American industrialists who traded with Germany, those who stood by as Germany invaded the Saar, Austria and the Sudetenland, and even Winston Churchill who wrote to the Times saying that in order to resist the German aggression, Britain needed a leader with the determination and leadership qualities of an Adolf Hitler.
As the Spencer Tracy character seeks to understand the German people he talks to servants and aristocrats, all of whom knew nothing of what was happening in the 'camps'. He doesn't believe a word of it. He accepts that there is a measure of guilt everywhere, but that doesn't lessen the guilt of the judges.
In a final confrontation with the Burt Lancaster character, the convicted judge pleads that he did not realise how it would end up, with so many millions dying. Tracy replies that it ended up like this the moment you sent an innocent man for execution.
Calvinist? Because it insists that everyone is guilty, and each is responsible for his own guilt. The pass mark is not lowered just because the standard is so low.
Sunday, December 14, 2008
A certain hope. I Peter chapter 1
On our return from San Francisco we found a flood. A water tank in the loft had overflowed. My daughter's bedroom ceiling was saturated, her carpet ruined, the underlay soaked and the floorboards wet. Perhaps worst was the fact that all her references for her PhD were turned to papier mache. Fortunately, we had taken out house and contents insurance a couple of weeks ago and the response from the insurers was great. (Take a bow, Swintons) The leak was repaired within an hour and next Wednesday a drying out company is coming. The carpet had to come up anyway for the electrician after Christmas. Most of the references have been retrievable from the internet, and the others should be obtainable for a couple of hundred dollars.
Then the washing machine broke. With a week's dirty washing this was very trying. I found a company I had never heard of in the Yellow Pages and a couple of hours later a technician called and replaced the brushes on our 5-year old Bosch and now it works well.
In I Peter 1:6-7 it says: In this you greatly rejoice, though now for a little while you may have had to suffer grief in all kinds of trials. These have come so that your faith—of greater worth than gold, which perishes even though refined by fire—may be proved genuine and may result in praise, glory and honor when Jesus Christ is revealed.
My first reaction was to say that many people have it worse than we had it. Christians throughout the world are suffering imprisonment, persecution, torture and beatings for their faith. Others have lost their homes jobs and livelihood. Some are orphaned, bereaved and killed. But that is not enough. It is little comfort for those who are suffering to say that there are some who have it worse. There may come a time when there is no-one worse off. No far better to realise that we have a living hope (verse 3). Whatever happens to us now, better things are coming.
As I look at the cricket score in India I might well say that I hope England win. India are being asked to score an unlikely total on the final day of the Test match and the odds are that England will attain a fine victory. But it by no means certain. Indian batsmen might score well and quickly; in Sachin Tendulka they have probably the finest batsmen in the world. Rain may intervene and force a draw or England's bowling might be innocuous and by blocking and defending India might hang on for a draw. The 'hope' referred to by Peter is not like that. It is more like the opposite of hopelessness. I could never expect to win an Olympic medal at clay pigeon shooting, however much I might hope to do so. I'm hopeless at that sort of thing. But if I open my front door after church and smell the meat in the oven, I not only hope for a fine dinner, I expect it. It is a certain hope.
Our certain hope does not depend on us but on the resurrection of the Lord Jesus (v3). If it depended on me I could well make a mess of it. I've been known to miss open goals in the past. But our salvation depends on Christ. He has already paid the price of our sins and in raising him from the dead, God has signaled that the sacrifice is sufficient. It is an inheritance that cannot perish, spoil or fade. Treasures that we lay up on earth perish. Have you ever disinterred an old dress or tie or suit that has been handing in the loft and found moth holes in it? The stitching has frayed or the colors have faded. Even metal objects will have tarnished. When I was young the pound was worth 2.84 dollars, now it is barely half that, and the dollar itself is pretty worthless. We talked about going into the Euro zone at 2 Euros to the pound, now it is close to parity. We invested in our house. Safe as houses, goes the saying. Our house has become a money pit. There is one inheritance that never fades, perishes or spoils; the salvation of our souls (v9).
This inheritance is kept in heaven for us (v4). It is not heaven itself. The Bible promises a new heaven and a new earth (Revelation Ch 21). Then, there will be no more death or mourning or crying or pain. Then, he will wipe every tear from our eyes. But if we die before the Lord returns we have a resting place with him in heaven (as he said to the dying thief - this day you will be with me in paradise) and when he returns those who die in Christ will rise first with new incorruptible bodies.
For Christ is our inheritance: to be with him, to hear him and see him and touch him. For all the beauty of San Francisco bay, it was worth much more to be able to share it with my wife. However beautiful heaven might be it would not be heaven without Jesus. It is to be with him that makes it heaven. A new heaven and earth that was just like the old one with the slate wiped clean would soon become corrupted again. The new heaven and earth will lack something that characterizes this one - sin.
There is a hope that stands the test of time,
That lifts my eye beyond the beckoning grave,
To see the matchless beauty of a day divine
When I behold his face!
When sufferings cease and sorrows die,
And every longing satisfied.
Then joy unspeakable will flood my soul,
For I am truly home.
Stuart Townend and Mark Edwards.
Then the washing machine broke. With a week's dirty washing this was very trying. I found a company I had never heard of in the Yellow Pages and a couple of hours later a technician called and replaced the brushes on our 5-year old Bosch and now it works well.
In I Peter 1:6-7 it says: In this you greatly rejoice, though now for a little while you may have had to suffer grief in all kinds of trials. These have come so that your faith—of greater worth than gold, which perishes even though refined by fire—may be proved genuine and may result in praise, glory and honor when Jesus Christ is revealed.
My first reaction was to say that many people have it worse than we had it. Christians throughout the world are suffering imprisonment, persecution, torture and beatings for their faith. Others have lost their homes jobs and livelihood. Some are orphaned, bereaved and killed. But that is not enough. It is little comfort for those who are suffering to say that there are some who have it worse. There may come a time when there is no-one worse off. No far better to realise that we have a living hope (verse 3). Whatever happens to us now, better things are coming.
As I look at the cricket score in India I might well say that I hope England win. India are being asked to score an unlikely total on the final day of the Test match and the odds are that England will attain a fine victory. But it by no means certain. Indian batsmen might score well and quickly; in Sachin Tendulka they have probably the finest batsmen in the world. Rain may intervene and force a draw or England's bowling might be innocuous and by blocking and defending India might hang on for a draw. The 'hope' referred to by Peter is not like that. It is more like the opposite of hopelessness. I could never expect to win an Olympic medal at clay pigeon shooting, however much I might hope to do so. I'm hopeless at that sort of thing. But if I open my front door after church and smell the meat in the oven, I not only hope for a fine dinner, I expect it. It is a certain hope.
Our certain hope does not depend on us but on the resurrection of the Lord Jesus (v3). If it depended on me I could well make a mess of it. I've been known to miss open goals in the past. But our salvation depends on Christ. He has already paid the price of our sins and in raising him from the dead, God has signaled that the sacrifice is sufficient. It is an inheritance that cannot perish, spoil or fade. Treasures that we lay up on earth perish. Have you ever disinterred an old dress or tie or suit that has been handing in the loft and found moth holes in it? The stitching has frayed or the colors have faded. Even metal objects will have tarnished. When I was young the pound was worth 2.84 dollars, now it is barely half that, and the dollar itself is pretty worthless. We talked about going into the Euro zone at 2 Euros to the pound, now it is close to parity. We invested in our house. Safe as houses, goes the saying. Our house has become a money pit. There is one inheritance that never fades, perishes or spoils; the salvation of our souls (v9).
This inheritance is kept in heaven for us (v4). It is not heaven itself. The Bible promises a new heaven and a new earth (Revelation Ch 21). Then, there will be no more death or mourning or crying or pain. Then, he will wipe every tear from our eyes. But if we die before the Lord returns we have a resting place with him in heaven (as he said to the dying thief - this day you will be with me in paradise) and when he returns those who die in Christ will rise first with new incorruptible bodies.
For Christ is our inheritance: to be with him, to hear him and see him and touch him. For all the beauty of San Francisco bay, it was worth much more to be able to share it with my wife. However beautiful heaven might be it would not be heaven without Jesus. It is to be with him that makes it heaven. A new heaven and earth that was just like the old one with the slate wiped clean would soon become corrupted again. The new heaven and earth will lack something that characterizes this one - sin.
There is a hope that stands the test of time,
That lifts my eye beyond the beckoning grave,
To see the matchless beauty of a day divine
When I behold his face!
When sufferings cease and sorrows die,
And every longing satisfied.
Then joy unspeakable will flood my soul,
For I am truly home.
Stuart Townend and Mark Edwards.
Rona Locke, RIP.
When I first began attending Lansdowne Baptist Church Trevor and Rona Locke were legends. As pioneer missionaries in India they were supported by the church. We sent them about £5000 a year. With that they supported themselves, their young son Justin, and about six other workers. They were translators. Trevor used to visit tribal peoples committing their languages to tape. Rona, the librarian, kept countless records on file cards (no computers in those days) and together they would transliterate the spoken languages and provide a written form so that reading primers and the Scripture could be provided for these native peoples. Together they were in much demand, not just as missionary speakers, but as the greatest experts in indigenous Indian languages.
Their son was a fine young boy. I remember the church bought him a bicycle when he was 13. He had already had a bike, but seeing a local pastor without one, he had given him his. He grew into a fine young man who married and had two children. A few years ago he lost his life while trying to rescue a drowning friend.
When Trevor and Rona returned from the mission field they could not afford to live in Bournemouth, but settled in Sheffield where house prices are cheaper. Here they began an outreach to Moslems. Trevor suffered a heart attack in Sheffield and following that they returned to their sending church here in Bournemouth.
In their latter years they remained active in the church and Trevor continued to visit the local mosque where his gentle and winning manner was accepted as he tried to win Moslems for Christ. Recently, Rona has suffered a series of strokes, which left her frustrated and she began to find it difficult to communicate. She died this morning. Even now she will be welcomed in heaven. Well done, good and faithful servant!
Their son was a fine young boy. I remember the church bought him a bicycle when he was 13. He had already had a bike, but seeing a local pastor without one, he had given him his. He grew into a fine young man who married and had two children. A few years ago he lost his life while trying to rescue a drowning friend.
When Trevor and Rona returned from the mission field they could not afford to live in Bournemouth, but settled in Sheffield where house prices are cheaper. Here they began an outreach to Moslems. Trevor suffered a heart attack in Sheffield and following that they returned to their sending church here in Bournemouth.
In their latter years they remained active in the church and Trevor continued to visit the local mosque where his gentle and winning manner was accepted as he tried to win Moslems for Christ. Recently, Rona has suffered a series of strokes, which left her frustrated and she began to find it difficult to communicate. She died this morning. Even now she will be welcomed in heaven. Well done, good and faithful servant!
Saturday, December 13, 2008
The Ashes of San Francisco.
Back from San Fransisco. This was my second visit, but I can't remember much about the last one except walking on the boardwalk at Pier 39 is warm sunny weather. This time we spent a week there and had more time to explore.
We stayed at Fisherman's Wharf which in winter is a quiet spot lacking the bustle of the Downtown area. The Shearaton was a perfectly acceptable hotel, though it lacks a proper restaurant. The skyscraper hotels in Downtown may have been plusher, but I disliked the crowds and shopping is not one of my pleasures. The weather was mostly fine, though we had one day of rain and overcast skies. Otherwise it was sunny with temperatures in the sixties. Early morning faogs were not really a problem for us.
The main attraction in SF is Alcatraz, which all visitors must see.Set just over a mile from the shore it was first a fort, then a military prison then a Federal one. Famous inmates included Al Capone, 'Machine-gun' Kelly and Robert 'Birdman' Stroud. Trick question: How many birds did Robert Stroud have at Alcatraz? Answer: None; he had them at Leavenworth. He used the birdseed to make alcohol and was refused birds when he did 'bird' on the island.
The cells were very small and 'D' wing where the prisoners were kept in darkness was particularly oppressive, though the cells were larger there. Did Frank Morris and his two colleagues really make good their escape as the Clint Eastwood film suggests? No-one knows, but their bodies were never found.
Muir woods, over the other side of the Golden Gate bridge is a forest of giant redwoods approached by a scary mountain road. The redwoods came in useful for construction during the gold rush, but were very flammable in 1906 when the earthquake set the city alight. With water supplies disrupted by the quake, the only way to control the fire was with a fire break. All the wooden buildings downtown of Van Ness Avenue were demolished. Jack London, the author of 'Call of the Wild'. sought to make money be replanting the forests felled for timber and bought in quick-growing eucalyptus trees from Australia. Unfortunately these are useless as lumber and he lost his money. Nevertheless their progeny abound in the woods and glades around San Francisco.
We took a bus tour round the city seeing Haight-Ashbury, the Victorian houses, the gay district at Castro, Lombard Street - the second crookedest street in America after Wall Street, and looked down on the city from Twin Peaks. We rode two of the trolley cars and took the 'F-train' in tramcars from Milan and Birmingham. The 1989 earthquake severely damaged the double-decker road around the bay, and rather than rebuild it, the city decided to replace it with a light railway and bought in disused tramcars from around the world.
After three days we ran out of things to do. The Science Museum was propaganda for anthropogenic global warming and neo-Darwinism, neither of which I believe to be accurate descriptions of our planet, though the aquarium is worth a visit.
San Francisco is no longer the largest city on the Bay - San Jose has that honor. In fact the size of SF has not changed much since the 1950s when I knew about these things.
In general, I found the Americans in San Francisco extremely pleasant and friendly. The food was difficult; lots of it but pretty tasteless. The eight-hour time difference meant that we couldn't go out in the evening and we started our day in deep darkness.
I think this will be the last time I visit the west coast; the journey takes too long and my metabolism finds it hard to cope with the jet-lag.
I shall write about the ASH meeting when I get over the time-shift and have collected my thoughts.
We stayed at Fisherman's Wharf which in winter is a quiet spot lacking the bustle of the Downtown area. The Shearaton was a perfectly acceptable hotel, though it lacks a proper restaurant. The skyscraper hotels in Downtown may have been plusher, but I disliked the crowds and shopping is not one of my pleasures. The weather was mostly fine, though we had one day of rain and overcast skies. Otherwise it was sunny with temperatures in the sixties. Early morning faogs were not really a problem for us.
The main attraction in SF is Alcatraz, which all visitors must see.Set just over a mile from the shore it was first a fort, then a military prison then a Federal one. Famous inmates included Al Capone, 'Machine-gun' Kelly and Robert 'Birdman' Stroud. Trick question: How many birds did Robert Stroud have at Alcatraz? Answer: None; he had them at Leavenworth. He used the birdseed to make alcohol and was refused birds when he did 'bird' on the island.
The cells were very small and 'D' wing where the prisoners were kept in darkness was particularly oppressive, though the cells were larger there. Did Frank Morris and his two colleagues really make good their escape as the Clint Eastwood film suggests? No-one knows, but their bodies were never found.
Muir woods, over the other side of the Golden Gate bridge is a forest of giant redwoods approached by a scary mountain road. The redwoods came in useful for construction during the gold rush, but were very flammable in 1906 when the earthquake set the city alight. With water supplies disrupted by the quake, the only way to control the fire was with a fire break. All the wooden buildings downtown of Van Ness Avenue were demolished. Jack London, the author of 'Call of the Wild'. sought to make money be replanting the forests felled for timber and bought in quick-growing eucalyptus trees from Australia. Unfortunately these are useless as lumber and he lost his money. Nevertheless their progeny abound in the woods and glades around San Francisco.
We took a bus tour round the city seeing Haight-Ashbury, the Victorian houses, the gay district at Castro, Lombard Street - the second crookedest street in America after Wall Street, and looked down on the city from Twin Peaks. We rode two of the trolley cars and took the 'F-train' in tramcars from Milan and Birmingham. The 1989 earthquake severely damaged the double-decker road around the bay, and rather than rebuild it, the city decided to replace it with a light railway and bought in disused tramcars from around the world.
After three days we ran out of things to do. The Science Museum was propaganda for anthropogenic global warming and neo-Darwinism, neither of which I believe to be accurate descriptions of our planet, though the aquarium is worth a visit.
San Francisco is no longer the largest city on the Bay - San Jose has that honor. In fact the size of SF has not changed much since the 1950s when I knew about these things.
In general, I found the Americans in San Francisco extremely pleasant and friendly. The food was difficult; lots of it but pretty tasteless. The eight-hour time difference meant that we couldn't go out in the evening and we started our day in deep darkness.
I think this will be the last time I visit the west coast; the journey takes too long and my metabolism finds it hard to cope with the jet-lag.
I shall write about the ASH meeting when I get over the time-shift and have collected my thoughts.
Monday, December 01, 2008
Carol Complete
Finally the carol is completed. The tune is O Holy Night.
Still was the night, the silent world was waiting
The time was right and the place was prepared.
Still in its sin and full of hurt and hating
The world was weak, but a rescue was dared.
God sent His Son, a baby frail and humble
In peril’s place, to suffer in our stead.
Oh! Child of hope; we tremble lest he stumble
In dangerous days. Oh! Child, in manger bed,
You hold our hope; Oh! Hope, hope of the world.
Men from the East, a Jewish king pursuing;
Menace increased as King Herod was roused.
Warned in a dream, his vicious plans undoing,
They would not tell where the baby was housed.
In frenzied rage the king began the killing;
The blood of every baby boy was shed.
Oh! Child of hope, in prophesy fulfilling,
To Egypt has fled; Oh! Child, in borrowed bed,
You hold our hope; Oh! Hope, hope of the world.
Still was the night, the garden finds him praying;
The moon was bright, but his friends fell asleep.
Will he escape, his Father disobeying?
His will is firm, the appointment he’ll keep.
Let Satan spit his venom vile and stinging,
Let torture split his body on the tree,
Oh! Child of hope, salvation he is bringing,
He crushes sin’s head; Oh! Child, in victory,
You hold our hope; Oh! Hope, hope of the world.
Still was the night, the silent world was waiting
The time was right and the place was prepared.
Still in its sin and full of hurt and hating
The world was weak, but a rescue was dared.
God sent His Son, a baby frail and humble
In peril’s place, to suffer in our stead.
Oh! Child of hope; we tremble lest he stumble
In dangerous days. Oh! Child, in manger bed,
You hold our hope; Oh! Hope, hope of the world.
Men from the East, a Jewish king pursuing;
Menace increased as King Herod was roused.
Warned in a dream, his vicious plans undoing,
They would not tell where the baby was housed.
In frenzied rage the king began the killing;
The blood of every baby boy was shed.
Oh! Child of hope, in prophesy fulfilling,
To Egypt has fled; Oh! Child, in borrowed bed,
You hold our hope; Oh! Hope, hope of the world.
Still was the night, the garden finds him praying;
The moon was bright, but his friends fell asleep.
Will he escape, his Father disobeying?
His will is firm, the appointment he’ll keep.
Let Satan spit his venom vile and stinging,
Let torture split his body on the tree,
Oh! Child of hope, salvation he is bringing,
He crushes sin’s head; Oh! Child, in victory,
You hold our hope; Oh! Hope, hope of the world.
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