Thursday, January 31, 2008

Fruits of the Spirit

Professor Howdy has a joke that he often recycles which purports to tell of a professor asking his class about opposites.

"What is the opposite of happiness?" "That would be sadness."

"What is the opposite of love?" "That would be hate."

"What is the opposite of woe?" he asks a particularly obtuse country bumpkin. "That would be giddy-yup."

Love, joy, peace, patience, kindness, goodness, faithfulness, gentleness, and self control are the fruits of the Sprit referred to in Galatians 5:22-3. If we have the Holy Spirit we have these fruits to show for it. Does that mean that if we do not have the Holy Spirit we will be full of hate, miserable as sin, given to warring, impatient, unkind, bad, unfaithful, rough and out of control?

You see, you have fallen into that trap haven't you?

If we lack the Holy Spirit we are not comic book villains. We are ordinary human beings. We walk by people in need, affecting not to notice. To be honest we don't really care much about Africa or Bangladesh; we are more concerned about what's happening to the economy.

We are not miserable. We're just not happy-clappy. There is enough in this world to get upset about and there seems to be no end to it. Sometimes things appear pretty hopeless, but perhaps Barack Obama will fix it (of Hillary or McCain or Romney).

We are not warlike, though if those Iranians continue to get uppity we might have to go to war. We're just a bit anxious about the future.

Silly to think of us as unkind. I treat people as I find them. If they're nice and polite, I can be reasonable too; but if they get aggressive with me I return it in spades.

I think of myself as a good man; I mean I pay my taxes and I wouldn't kick a dog or anything.

I'm faithful to my wife. There was that time at the office party, but that was just a snog; it didn't mean anything.

I wouldn't call myself rough and unthinking; mind you I'm nobody's sissy. I call a spade a spade and don't suffer fools gladly.

I suppose I've got a temper, but you have to provoke me. I don't go around shouting the odds, but sometimes - I mean that Bill O'Reilly (or Dan Rather if you’d rather).

The fruits of the Spirit are positive virtues. They are supernatural virtues. When we behave like normal human beings, they are missing.

Wednesday, January 30, 2008

Can I write fiction?

One of the things I am going to do in my retirement (if I get any encouragement) is write fiction. Here is the first page.


Leukaemia isn’t a children’s disease. That’s just the fund-raisers’ bullshit. The pathetic little girl with no hair and black rings round her eyes makes good advertising copy, but it’s nowhere near the truth. Sure, we can cure a lot of kids these days, but mostly it’s a disease of old people.

The guy in front of me was typical. At seventy-four going on a hundred and fifty, he was grey and getting greyer. The bead of sweat on his upper lip could have been nervousness, but probably it was part of his illness. I’m sure it wasn’t because he recognised me. How could he? I’d grown up since then.

I’d recognised his name at once. Ronald Gottings – Ronnie; it’s unusual enough to encounter only once in a lifetime. I tried to recall his face as it was then, but it wouldn’t come. Memory is capricious.

It wasn’t my earliest memory; that would have been a visit to my great-grandmother’s house. She died before I was two and I can’t envisage her at all. I remember sitting on my daddy’s knees (I was still in napkins) and being asked if I wanted to play the piano. Who knows what a piano is when you're less than two years old? I was more interested in the radio on top of it, made of cream-coloured Bakelite. I knew I wasn’t allowed to touch the radio. Was “piano” like “radio” another word for wireless? I was confused and embarrassed and kept silent, which irked Daddy because he was there to show off his clever blond baby to Mummy’s grandmother.

I heard later that there was Jewish money there, but we never saw any of it. Mummy had skivvied there during the thirties, washing the old lady’s feet because she was too fat to reach them, and scrubbing the floors.

We were still very poor when I first met Ronnie. We lived in a one-bedroom basement flat across the road from the park. The Memorial Gardens was their proper name. The centrepiece was twenty-foot granite obelisk on which was carved the names of the fallen in the Great War. When I first met Ronnie they were writing the names of those killed in the second War and people were beginning to worry if there would be room enough for those killed in the next one.

The flat was very dark, quite cramped for the four of us – my baby sister had been born by then – and we had no garden, just a small yard surfaced with red house bricks and drain covers. We played in the park. There was next to no traffic then and always plenty of kids about. I guess there were bats and balls, and older girls who took us for walks. I was still a very pretty kid and more available than dolls. Ronnie was someone that the older boys talked about. He’d been to the war and come back.

I first saw him sitting on one of those green slatted park benches they used to have. He was surrounded by the other boys and smoking a Woodbine. I still can’t bring his face back. His jacket had leather patches on the elbows and his trousers were brown corduroys. The trouble with memory is trying to work out how much is true. Are we remembering what happened or simply our last memory of it? It’s like that prompt that comes up when you close down your word processor. Do you want to save the changes you made to this document? You didn’t know you’d made any changes. How much do we corrupt a memory every time we take it out and look at it before we put it away again? Alright, I couldn’t swear to the leather patches but I’m certain of the corduroys.

He seemed very tall, then. He wasn’t tall now, barely five foot seven, and stooped shorter. His doctor’s letter told of heart disease and alcohol abuse. His fingers told me the Woodbine habit had never died. His wife had had him back a fortnight previously. He’d been away for just a month this time. The tobacco and stale sweat smell were very familiar to me. Smokers get leukaemia twice as commonly as non-smokers.

There is no easy way to break the news. “Mr Gottings, I’m afraid that you’ve got leukaemia. I’m very sorry.”

His wife sucked in her breath and started weeping, but he said nothing. He still stared at the desk and wouldn’t meet my eyes.

“There are several types of leukaemia. This one is called acute myeloid leukaemia. We call it AML for short. I’m afraid it’s one of the worst sort.”

Funny how we use that word “afraid”. What was I afraid of? Not of Ronnie Gottings, though I had been once. Afraid of breaking bad news? I’d done it so many times. Afraid of hurting Ronnie? Afraid of Ronnie’s retribution? Better drop the “afraid”.

“Leukaemia is a sort of cancer of the blood cells. It grows in the bone marrow. You need to make about three million blood cells every second. Because the leukaemia is growing there you can’t make the good cells. Because you’re short of good white cells you’re liable to infections. You can’t make enough red cells either, that’s why you’re feeling tired and short of breath.”

“Is that where the white cells eat up the reds?”

They always say that. His wife was younger than him by more than twenty years, younger than me, even. She had that faded pepper and salt hair and slightly sagging skin that you see on women who have started to make an effort again after years of not trying. She’d put on a smart navy suit to contrast with Ronnie’s scruffiness.

He spoke for the first time. “Am I gonna die, doc?”

We’re all going to die. They ask us that stupid question as if we were soothsayers. Doctors see it as a trap; if we say they have a year, they die next week and the relatives complain. If we tell them they’ll be dead in a month they live for a year out of spite.

“They told me I’d die when I had the by-pass operation.” See what I mean.

“What have you done with your life? What was your job?”

“I’ve travelled a lot. Africa, Bangkok. Got the taste for it in the army.”

“You were in the war?”

“We all were, weren’t we?”


Let me know if you think I should continue.

Tuesday, January 29, 2008


'Natural' is a word that raises my hackles. A story is told of an old gardener who was confronted by the local parson who admired the garden.

"You and God have made a beautiful spot together." said the parson.

"Oh Ah," replied the gardener, "but you should have seen it when he had it to himself!"

Everything that's natural is supposed to be somehow superior, but even the bucolic scenes of yesteryear that we so admire were the product of technology. My attention was recently drawn to an aerial picture of the border between Israel and the Gaza strip. The land on the Israeli side has been tilled and planted, watered and harvested. The neat strips are the effect of applied technology. On the Palestinian side and indeed the Egyptian side, the absence of technology leaves chaos.

TB is natural and so is malaria. So is HIV. You don't need to postulate man-made global warming to inflict harm on the poor. Natural phenomena do it well enough.

Snakes are natural and so are crocodiles. So is the funnel web spider. The natural tiger will kill you given half a chance; so will the lion. Natural influenza in 1918 killed more people than the technological guns and bombs of the massed armies in Europe.

We live in a technologically replete world. There is no going back to horsepower, poultices and nightsoil. The chemicals we use are refined and pure, not the nasty, foul smelling mixtures our forefathers used.

Cold caves and contaminated springs are natural. We have insulated houses and clean water because of technology.

It seems that the world is warming. I would bet that it is a natural event rather than a technological disaster. The remedy won't be Luddism but technology.

CLL is a natural disease. The remedy won't be natural herbs, either as infusions or enemas, but technological chemicals cleverly directed at the natural disease by man's ingenuity.

Sunday, January 27, 2008

Funeral Fable.

Maria lives in a village in South America with no water. Everyday she must walk 5 miles to the spring to fetch water. She carries her two water pots, Santos and Pueblo, suspended from a yoke across her shoulders. As she nears home her burden becomes lighter, because Pueblo is a cracked pot and water leaks out of him. By the time Maria reaches the village, Pueblo is only half full.

Pueblo is a very unhappy pot. He says to Maria, "I am so sorry that I cannot serve you as Santos serves you. You walk all that way to fetch water, but when we return I only bring half as much water as Santos brings."

Maria consols him, "Look at the path. You will see that all along the path are beautiful flowers that cheer me as I make the long journey. But the flowers are only on one side, the side that you water."

"Pueblo," she continued, "I know you for what you are and I decided to use you. I brought seeds and dropped them on the gound that you had watered. So even though you are not perfect and leak a little, I was able to use you to bring cheer and happiness to all who walk along this path."


"Even if I have to die with you, I will not disown you." said Simon Peter.

Were you there when they crucified my Lord?

"Simon, carry my cross."

And Simon stepped forward. The Cyrenian was recruited to Jesus' cause when Peter had deserted him. The Carpenter must have been used to carrying wooden burdens, but the scourging had weakened him. He could have called on Angels to assist him. Instead, someone chose a North African, the father of Rufus and Alexander; the same Rufus of whom Paul wrote, "Greet Rufus, chosen in the Lord, and his mother, who has been a mother to me too."?

"Let one of us sit at your right and the other at your left in your glory." demanded James and John.

"You do not know what you are asking," Jesus said, "Can you drink the cup I drink or be baptised with the baptism I am baptised with?"

"To sit at my right or left is not for me to grant. These places belong to those for whom they have been prepared."

Were you, James and John, there when they crucified my Lord?

They crucified two robbers with him, one on his right and one on his left. Those who were crucified with him also heaped insults upon him.

Everyone had deserted him and fled. He was alone on the cross. One by one the prophesies were fulfilled. "Scorned by men and despised by the people. All who see me mock me; they hurl insults, shaking their heads. I am poured out like water, and all my bones are out of joint. My heart has turned to wax; it has melted away within me. My strength is dried up like a potsherd and my tongue sticks to the roof of my mouth. A band of evil men surround me, they have pierced my hands and my feet. I can count all my bones; people stare and gloat over me. They divide my garments among them and cast lots for my clothing. His appearance was so disfigured beyond that of any man and his form marred beyond human likeness. He was despised and rejected by men, a man of sorrows and familiar with suffering. Like one from whom men hide their faces he was despised and we esteemed him not. He was pierced for our transgressions and crushed for our iniquities and the punishment that brought us peace was upon him and by his wounds we are healed."

Were you there? No, of course not. Would you have been there? Only among the scoffers. Will you be there? By God's grace.

Give us the grace, O God, to stand alongside Jesus, to walk beside Him, to carry our crosses, to accept suffering and not to complain, to show forth His glory.

Saturday, January 26, 2008

An annoying phrase

Am I alone in being irritated by the phrase, "We and others have found..."? You see it often in scientific papers, often those written by the also-rans. Whereas a work of art is often a unique conception, in science it seldom is. If you read the literature and are au fait with current scientific thought you can often predict what the next discovery will be. There are only so many possibilities and the application of the right technique will often reveal the answer. The discovery of the JAK2 mutations in myeloproliferative disease is a good example where several labs published the discovery at around the same time. Who first had the idea is obfuscated by the noise of many papers. Of course, this sort of thing is often a bit of concealed fraud, because nothing gets published without the refereeing process and referees have been known to delay a paper until they have dupilcated the work themselves.

To write, "We and others have found..." is not so great a sin, but it makes 'self' more prominent than is fair. You may wll have been in the race and only chance has made you second or third or sixteenth, but a more correct summary might be, "Others have found and we have confirmed...".

You see, even in science a little bit of genius is sometimes required.

Toothless punishment

Wailing and gnashing, a just desert
For long lives spent inflicting hurt.
But for the toothless what’s beneath?
The answer is, of course, new teeth!

First encounter

Do you recall the silver street
The moon had painted on the lake?
At last the contact was complete
And mutual signals no mistake.

Do you regret the hurried start
As time accelerated by?
Poorly prepared, the flurried heart
Confuses ‘how’ with ‘when’ and ‘why’.

What language is sufficient for
The first approach of tenderness?
Between the ‘like’ and ‘je t’adore’
Words hover like a brief caress.

What sorcery has been at play
To cast all cautious care adrift?
No magic but the nerve to stay,
To take and tender such a gift.

What future for this orphan heart?
And can it stay still far away?
But what could force it to depart,
When I have watched your eyes all day?

Friday, January 25, 2008


The mean corpuscular volume is the most important of the red cell indices. It measures the average size of the red cells.

A red cell is mainly made of hemoglobin with a membrane to go round it. Small round cells are caused by a lack of hemoglobin. There are only three causes of small red cells - there are two causes of too little hem and one cause of too little globin. The amount of hem is controlled by iron and the amount of globin is controlled by the genes you inherit from your parents. If you inherit dodgy globin genes you have thalassemia. There are several sorts, but they all result in small red cells.

If you have too little iron you can't make hem and you end up with small red cells. Too little iron may be the result of too little iron in the body - either because of not enough iron in the diet, which is very rare in most Western countries, or because of excessive iron loss - mainly due to bleeding. But too little iron for the red cells can be caused by the macrophages greedily hanging on to it and not releasing it to the forming red cells in the bone marrow. This happens with a wide variety of chronic disorders such as Crohn' disease, ulcerative colitis, rheumatoid arthritis, chronic infection and some cancers.

Raised MCVs have more causes. Everybody knows about megaloblastic anemia due to a deficiency of either folic acid or vitamin B12. These are relatively easy to diagnosed and it is important to rule them out by measuring B12 and folate levels, but in actual fact, these are relatively rare cause of macrocytosis, as too are the floppy membrane diseases - conditions where the size of the red cells is increased because there is too much membrane. Examples would be liver disease and thyroid deficiency. Alcoholics have large red cells, probably for a variety of reasons, and probably the commonest cause in older people is MDS.

However, we sometimes see raised MCVs in CLL and none of these reasons apply. I think that whatever fills the bone marrow spaces that shouldn't be there causes an increase in the MCV. You certainly see it in myeloma, but why this should be is unknown.

Sunday, January 20, 2008


The graffito was discovered in 1857, when a building called the domus Gelotiana was unearthed on the Palatine Hill. The emperor Caligula had acquired the house for the imperial palace, which after Caligula died became used as a Paedagogium or boarding-school for the imperial page boys. Later the street on which the house sat was walled off to give support to extensions to the buildings above, and it thus remained sealed for centuries. The graffito is today housed in the Palatine antiquarium in Rome. Said to date from the third century AD, some scholars put it as early as 85 AD, just six years after the destruction of Pompeii.

The image depicts a man with the head of a donkey who appears to be attached to a cross. To the left is a young man raising one hand in a gesture suggesting worship. The inscription reads "Alexamenos worships his god". The general consensus is that the graffito dates from some time in the third century, although dates as early as AD 85 have been suggested.

The idea that Christians worshipped a man born of a donkey who was judicially executed was quite a common one in the Roman Empire. The early Christian Father, Tertullian, wrote about it, "In this matter we are [said to be] guilty not merely of forsaking the religion of the community, but of introducing a monstrous superstition; for some among you have dreamed that our god is the head of an ass, an absurdity which Cornelius Tacitus first suggested",

In Mark 15:16-20 Jesus was mocked by the Roman soldiers. They dressed him up in an old scarlet robe that had turned purple with age, they plaited a crown from thorns and placed it on his head and gave him a staff in his hand as a mock sceptre. They bent down and called out to him, "Hail, Jesus, King of the Jews!" Then they took the staff and beat him about the head repeatedly with it and spat upon him.

Mockery is too mild a word for it. It sounds like a bit of tomfoolery, badinage or banter, but this was vicious. Ridicule, derision, insult; those are more appropriate terms. The soldiers weren't just drawing a caricature or making catcalls, they were bullying Jesus in a humiliating way. A crown of thorns is painful and draws blood. Beating around the head with a stave hurts. Remember this was a man who had just been flogged.

Some Christians with tender consciences read this and think, "Is my worship of God a mockery?" When I sing "All to Jesus, I surrender," am I guilty of mockery because I know I hold things back?

The answer is no. This passage is not directed at them. It is pointed at unbelief. Unbelievers still scoff at Jesus and those who follow him. Why is that? Who scoffs at Hindus? Who laughs at Buddhists? Mike Huckabee draws the ridicule of the BBC but Mitt Romney doesn't. Why is that? Who makes jokes about Moslems? (Who would dare?) If they mocked Christ, why would they stop at his followers? The Alexamenos graffito demonstrates that this is something that has always gone on.

How should we react? When the BBC decided to screen "Jerry Springer - the Opera" there were more protests from viewers than for any program ever. The BBC rejected the complaints and this was upheld in the High Court and the Court of Appeal. When Danish cartoonists drew cartoons that mocked Mohammad there were worldwide violent protests by Moslems and the media, for the most part, caved in.

How did Jesus react? He stayed silent and absorbed it. Don't doubt he could have called down legions of Angels. He could have made these mockers scorched shadows on the earth. Yet he withheld his power. Later on the cross he was to pray, "Father, forgive them, for they know not what they do."

A story is told of a group of people standing in line awaiting the opening of a bank at 9 a.m. when a man walks straight to the front of the line and is first in to be served. The people waiting in line make no protest. You see the man who queue-jumped was carrying a white stick and was guided by a dog. He was blind to the fact that there was a line.

Jesus was not willing to punish people for ignorance. There will come a time when they will be judged, but there was a time when we were ignorant. If we understand why the man queue jumped we are able to forgive him. Jesus looked at the scoffers and understood them and loved them. He loved them so much that we died for them.

Do you love your enemies? Do you do good to those who despitefully use you? When people mock you for being a Christian, forgive them, love them, pray for them.

Saturday, January 19, 2008

A full month.

I am flying to Boston the day after tomorrow for a couple of days. This is to do with a Campath trial that I am helping to supervise. I have almost completed a similar role in a rituximab trial and will be traveling to Frankfurt in a couple of weeks for a similar meeting. After a long career treating patients and organizing a health service, my life has moved on. January has been a very busy month, but one that is very different from what I have done most Januaries in my career. I have done a good deal of refereeing. Several medical journals including Blood, British Journal of Haematology and Haematologica have sought my advice on publishing different scientific articles. This is a difficult task. Reading the paper is often hard work. Then you have to test it for scientific validity, then you have to consider it in the context of what has already been done. Is it novel? Or just confirmatory? Is it mere repetition? Finally, is it important or merely trivial?

Then I have reviewed a couple of grant proposals (and still have two more to do). This is a responsible task. Someone's livelihood is at stake, but often the cash to support them is hard won - someone has been shaking an awful lot of tins.

Then there is GTAC. I have served on the Gene Therapy Advisory Committee for 6 years. These proposals are even more complicated. The science is very hard, but more than that the proposed treatment is potentially lethal. We are not only a scientific review committee, but also an ethical committee. I have reviewed two GTAC proposals this month and have a meeting coming up before the end of the month to discuss the future of the committee. Should we expand or limit our activities? Have some sorts of gene therapy now become routine? Are we able to take on stem cell therapy?

Then I have been editing Leukemia Research. this involves selecting referees for submitted papers (I have had 25 so far this month) and when teh reviews come in, deciding whether or not they should be published.

I also finished off a chapter I was writing on MDS and started a new one on CLL.

I have also spent time this month in my capacity of Treasurer of the MDS Foundation, trying to set up a Euro account that can be manipulated over the Internet. This seems impossible.

Quite apart from these intellectual activities, I have this month cleaned out the gutters on one side of the house, helped my daughter move out of her apartment, twice swept the drive of fallen leaves, been to the gym nine times, read the latest fantasy novels of Terry Goodkind and Stephen Donaldson and the Iain Banks novel 'Dead Air', watched the first two of the Helen Mirren 'Prime Suspect' series and watched the Justine Waddell version of 'Tess of the d'Urbevilles'.

Wednesday, January 16, 2008

Lancet lies

Back in 2006 in time to influence the congressional election the Lancet published a report estimating that the casualties in Iraq had exceeded 650,000. At the time I reckoned this to be a load of hogwash. Last week the Wall Street Journal published an article about the report. It turns out the Lancet study was funded by anti-Bush partisans and conducted by antiwar activists posing as objective researchers.

The Lancet death toll was more than 10 times what had been estimated by the U.S. and Iraqi governments, and even by human rights groups. It now appears that the Lancet study was funded by billionaire George Soros's Open Society Institute. Mr. Soros is a famous critic of the Iraq campaign and well-known partisan, having spent tens of millions trying to defeat Mr. Bush in 2004. Soros made much of his money by speculating against the pound sterling, forcing it out of the European monetary system.

Two co-authors of the report, Gilbert Burnham and Les Roberts of Johns Hopkins University, told the reporters that they opposed the war from the outset and sent their report to the Lancet on the condition that it be published before the election.

Lancet Editor Richard Horton agreed to rush the study into print, with an expedited peer review process, without seeing the surveyors' original data. I have met Richard Horton and took an instant dislike to him. He spoke at a meeting of the European Association of Science Editors that I attended. At first I thought it was just his youth that made him a conceited show-off, but as he has grown older I see that this is his nature. I cancelled my Lancet subscription shortly afterwards. Here's a quote from him, "The axis of Anglo-American imperialism extends its influence through war and conflict, gathering power and wealth as it goes, so millions of people are left to die in poverty and disease." You might remember Horton as the man who published the scandalous lies about the MMR vaccine.

The key person involved in collecting the Lancet data was Iraqi researcher, Riyadh Lafta, who has failed to follow the customary scientific practice of making his data available for inspection by other researchers. Mr. Lafta had been an official in Saddam's ministry of health when the dictator was attempting to end international sanctions against Iraq. He wrote articles asserting that many Iraqis were dying from cancer and other diseases caused by spent U.S. uranium shells from the Gulf War. These too were politically derived lies.

Tuesday, January 15, 2008

What sort of theologian are you?

What sort of theologian are you?You might like to try this questionnaire. I came out as somewhere between Karl Barth and St Anselm, and nor very different from Martin Luther and Jean Calvin.
That link doesn't seem to work. Try

Different religions; different roads

All roads lead to God don't they?

Christianity is different from other religions. In every other religion you are required to do something for God. In Christianity God has done something for you.

All roads don't lead to God. Remember those puzzles we used to do as children, where a jumbled maze of lines had many entry points, but only one led to the prize? Some of the lines came very close, only to veer away at the last moment. In the Sermon on the Mount Jesus talked about a broad road that led to destruction which had many people on it, and a narrow road that leads to life which only a few find.

Jesus is very exclusive. "I am the way the truth and the life;" he said, "no one comes to the Father, but by me."

Note that it is to the Father that Jesus is taking us. In John's gospel we read, "Yet to all who received him, to those who believed in his name, he gave the right to become children of God." If Jesus is the one and only son of God, how can we become children of God?

The answer is simple; He adopts us.

People have favorite chapters in the Bible; among mine are Ephesians 1 and Romans 8. In both Paul writes of our adoption as sons. "In love he predestined us to be adopted as his sons through Jesus Christ." and "We wait eagerly for our adoption as sons."

Unadopted roads soon become shabby as lack of maintenance leads to puddles and potholes. Adopted roads are well maintained and you reach your destination safely.

Some complain that this is too exclusive. What right has he to hide this road from the great mass of people who take the broad road? But the entrance to the narrow road is not hidden. It is not a concealed entrance, it is as plain as can be. Goodness me there are crosses everywhere! It is not hidden, but it is very low and you have to stoop to get through. All it requires is to get down on your knees and recognize that there is nothing you can do to save yourself. Then accept it; it is a gift.

God is not willing that any should perish and He has done everything necessary to save everyone. This is not like the Titanic where there were not enough lifeboats, and it is not a case of women and children first, though in many churches it seems like that. But He will not force anyone into the lifeboat. If you prefer to swim for it on your own He will just warn you that you will not make it; if you escape the sharks, the freezing water will get you.

Monday, January 14, 2008

Are you saved?

Some people resent the question; others are amused by it. What am I supposed to be saved from? An onrushing train?

We are saved from sin. Sin is a term in archery that means 'missing the target', especially by falling short of it. Paul writes to the Romans, "for all have sinned and fall short of the glory of God". It's worse than that, for he goes on to write, "For the wages of sin is death".

God has set a standard and the pass mark is 100%. Here's a challenge: try and live a perfect life. Give up? I tried and couldn't do it. Just one sin is all it takes. Miss the bullseye just one time and you fall short of the standard required.

There is a story of Moses coming down from Mount Sinai and saying to the Children of Israel, "It's no good; I couldn't get him to budge over the adultery thing, but I did manage to get us one day off a week."

Moses was given the Law, not so that we could live by it but to show how impossible it is. Because some people believed they could, Jesus demonstrated how superficially they were interpreting the commandments. Murder? It's as bad to be angry against your neighbor. Adultery? Whenever you look at a pin-up or fantasize over a film star you've as good as done it already. This is Paul to the Romans again, "There is no one righteous, not even one." Jesus saves us from sin because he did live a completely sinless life. Someone once said to me, "I am not phased by the resurrection or by any of the miracles, but I can't believe that anyone could live a sinless life." The Bible tells us that Jesus did just that, and here's the proof: when they tried to kill him, Death spat him out again. Death is the wages of sin, not sinlessness.

Sin is something we need saving from and there is only one savior.

We are saved from the presence of sin, but also from the power of sin. Once we have a grip on Christ (or rather He has a grip on us) sin loses its attractiveness. It doesn't happen all at once, but the things that used to enthrall us begin to seem petty dull. Of course, they don't go overnight; some of them are hooked into us pretty deep. Some of them we have to pray pretty hard about. But even though we might still fall for them we begin to hate ourselves for doing so. Once you have been saved you can never be a happy sinner again. Take it from me, you'll never be completely free from sin in this life. There's a story told of a dinner guest of CH Spurgeon who proudly told his host that he had at last achieved sinless perfection. Whereupon, Spurgeon chucked a jug of water over him. The man's temper flared, "What do you think you are doing?"

"It's as I thought," said Spurgeon, "the Old Man's not dead, just sleeping."

In order to free us from the power of sin Jesus sent His Holy Spirit when he returned to heaven. It's the Spirit's job to sanctify us, to strip away the sin and make us fit for heaven. It can be a hard job and painful when we resist Him, but it's worth it.

There should always be three 'P's and the third one is punishment. Jesus saves us from the punishment of sin. God's wrath, they used to call it, though 'wrath' is a very old-fashioned word. What it means is God's righteousness in action. It's fashionable these days to think of it as a sort of involuntary reaction, like 'nature abhors a vacuum'. Vacuum flasks consist of a double layer of silvered glass with nothing in between - no air, no nitrogen, no oxygen. Smash the glass and the whole thing implodes. The air rushes in to fill the empty space, sucking the broken glass in with it. People say that God's nature is such that He abhors sin, and that He can't be in the same place as sin. they say that His wrath is His natural reaction against sin.

But I think that that is a lame attempt to absolve God from being angry. God is angry. There is such a thing as righteous anger. Suppose you saw a pedophile torturing a child, would you not be angry? There is nothing evil about being angry at such a happening. That is righteous anger. And God is angry at sin. Why are there young women from Eastern Europe in London working as prostitutes? It's because of sin. Why are there children in Africa starving? It's because of sin. Why are children cast into care as their parents' marriage is broken up? It's because of sin. Why are young black kids gunned down on the streets of our cities? It's because of sin. It's wholly right to be angry about these things. We mustn't think of God as just a passionless force; He has feelings.

And the greatest of these feelings is love. He loved us so much that He sent His one and only son to receive the punishment for our sin in His own body. This wasn't 'child abuse' as Richard Dawkins called it. Jesus volunteered for the job. There was no difference between the pain of the son and the pain of the father. What was described for us in the Bible in the flogging and crucifixion was a picture of the greater desecration of the Godhead torn asunder. Jesus cried out, "My God, my God, why have you forsaken me?" but what was God the Father feeling at that moment? We can perhaps try to imagine what it is like for Jesus to be separated from His father; it is sometimes called a cry of dereliction. We think of abandonment. Hell is said to be the total and absolute separation from God. When we say that Jesus went through Hell for us, we can begin to imagine what it meant. But how can we imagine what it was like for the Father?

I think of a mother whose baby is ripped from her womb by a Janjaweed bayonet in Darfur. I think of a mother whose child is stolen from her bed as she slept by a pedophile. I think of a father and son at sea when the son is lost to a mighty wave. I think of the parents of that beautiful, Godly young man stuck down and murdered by drunken louts on his way home. I think of the mother who sees her daughter bleeding in the bus queue when a drunken driver has ploughed into her and her baby carriage. I think of the father holding the hand of his dying daughter blown up by a terrorist bomb in Enniskillen. None of these real incidents is enough.

Our salvation is precious because it was bought at such a price.

How deep the Father's love for us,
How vast beyond all measure
That He should give His only Son
To make a wretch His treasure

How great the pain of searing loss,
The Father turns His face away
As wounds which mar the chosen One,
Bring many sons to glory

Behold the Man upon a cross,
My sin upon His shoulders
Ashamed I hear my mocking voice,
Call out among the scoffers

It was my sin that held Him there
Until it was accomplished
His dying breath has brought me life
I know that it is finished

I will not boast in anything
No gifts, no power, no wisdom
But I will boast in Jesus Christ
His death and resurrection

Why should I gain from His reward?
I cannot give an answer,
But this I know with all my heart
His wounds have paid my ransom

Stuart Townend

Sunday, January 13, 2008

Transplants in CLL

I thought you might be interested in this provisional guideline for when to do a transplant in CLL.

1. Very high risk CLL defined as CLL with >20% cells showing del 17p or purine analogue refractory. These patients should be treated with p53 independent therapy such as high dose methyl prednisolone and/or alemtuzumab to maximum response and then allografted if possible in first complete remission.

2. High risk CLL defined according to EBMT criteria:{Dreger, 2007}
(i) Relapse within 6 months of Purine Analog therapy
(ii) Relapse within 2 years of intensive therapy including Purine Analog/alkylator combinations, chemo-immunotherapy or autologous transplantation, in second complete remission.

3. Richter's transformation in first complete remission.

It would be standard therapy to treat all of these categories of patients with either a sibling or volunteer matched transplant with reduced intensity conditioning.

4. Other indications. Includes patients not fulfilling criteria 1 or 2 who are in second or subsequent relapse with at least one of the other commonly recognised adverse features listed below:
(i) Bone marrow failure according to Binet criteria
(ii) Unmutated VH genes (<98% germline or V3.21)
(iii) ZAP 70+ (>20%)
(iv) CD38+ (>7%)
(v) Del 11q

For this category a reduced intensity conditioning sibling or volunteer donor transplant is not standard, but might be ordered by a CLL expert.

Umbilical cord blood transplants are experimental and should only be performed in the context of a clinical trial in patients for whom no adult donor is available.

Autografts are generally not recommended.

A sense of justice

When I came home from church I flipped on the TV to find them showing an old Audrey Hepburn film, "How to steal a million". Gentle stuff - one of those 'caper' movies that were so popular then. The sex comprised a very chaste kiss with Peter O'Toole and nobody profited from the crime.

Back then that was the rule. In the movies no-one was allowed to get away with it. Life isn't like that. Most crimes go undetected and unpunished.

I remember a TV series back then which starred Margaret Lockwood as a barrister (courtroom attorney for the Americans). A rich guy employed her to defend him in a drink-driving case. After he was acquitted he received her bill. He commented, "That's an awful lot to pay for justice."

She replied, "But you didn't get justice, Mr Smith, you got off!"

You may have gathered that this is just a roundabout way of introducing Mark chapter 15.

Pontius Pilate wasn't much concerned with justice either, he was concerned with order. We don't know much about Pilate. He was for 10 years Prefect of the Roman Province of Judea but where he came from and how he died are the subject of myth and legend. He was canonized by the Ethiopian Church and his wife was canonized by the Coptic Church. At various time he has been blamed and exonerated for the death of Jesus. An inscription found in 1961 confirms his historicity. We have to answer the question of how Matthew knew of his wife's dream, so perhaps there is some truth in the suggestion that she at least was converted afterwards.

Jesus did not defend himself. The NIV translation, "Yes, it is as you say." is a disputed one. The NASV has "It is as you say.", the KJV "Thou sayest it.", the Good News Bible "Those are your words,", The Message "If you say so."

If I were to paraphrase it, the sense is, "You're not wrong, but I wouldn't put it like that."

There are two reasons why Jesus does not defend himself. One is to fulfil prophesy, "as a sheep before her shearers is silent, so he did not open his mouth." Isaiah 53:7, but the other reason is that the death of the Christ had to be voluntary. If he was killed simply as a result of an injustice then he would not be a substitute; he would just be another martyr.

The Jews were familiar with the idea of a substitute. Every day there were sacrifices in the Temple. A lamb or a bull or a couple of pigeons were killed as a substitute for somebody's sins. But they could not suffice. As the writer to the Hebrews put it, "The law is only a shadow of the good things that are coming — not the realities themselves. For this reason it can never, by the same sacrifices repeated endlessly year after year, make perfect those who draw near to worship. If it could, would they not have stopped being offered? For the worshippers would have been cleansed once for all, and would no longer have felt guilty for their sins. But those sacrifices are an annual reminder of sins, because it is impossible for the blood of bulls and goats to take away sins." Hebrews 10:1-4.

Barabbas could not have been the substitute. Everyone knew that Barabbas was guilty. But everyone knew that Jesus was innocent. Pilate knew, "it was out of envy that the chief priests had handed Jesus over to him." (v 11) The sacrifice had to be of a lamb without blemish, a picture of the sinless Christ. Pilate released Barabbas to appease the crowd and then asked the same crowd, "What shall I do with Jesus?" In many ways it is the perfect question.

What will you do with Jesus? What you can't do is watch and wait. Just as with CLL you can watch and wait too long. There will come a time when it is too late for decisive action. A famous atheist was asked what he would do if he met the risen Christ after death. He replied that he would complain to him, "Sir, you did not leave enough evidence."

To see the question of Christ as a puzzle that can be solved by scientific experiment or the application of reason or by the experience of life is a conclusion of arrogance. All that is required is a simple faith; something available to the peasant who walks behind a plough in Patagonia, the child who sits in an mud hut in Malawi, the factory worker in Pittsburgh, the Inuit in an ice-hut in Alaska, or the banker in a board room in Manhattan. "Where were you when I laid the foundations of the earth?" asks God of Job when the patriarch dared to question Him.

Pilate was found wanting. He handed over Jesus to be flogged and crucified. If you have seen "The Passion of the Christ" you don't need a description of a Roman flogging. If you have a tender soul don't watch it. It was criticised by many as revelling in the blood. All I can say is that the research for the film was accurate.

We cannot imagine the pain of crucifixion. The word 'excruciating' derives from it. There is a Latin verb cruciare which means 'to torment'.

Have you been found wanting. Are there occasion when you did not do what was right because you needed to 'please the crowd'? Do you squirm when you think of them? I do.

Friday, January 11, 2008

What is a Christian?

What makes a Christian? Most people believe in God, but the God they believe in is often some mystical being about whom they have very little knowledge and understanding. They may turn to the Church, but how do they know whether what the church says is true when different churches say different things? And why believe in the Christian God? Why not follow Islam or one of the Eastern religions?

How can anyone, simply by looking at the world know God? Sure, you might see a pattern in creation and assume a creator. Sure you might look at your inner feelings of justice and right or wrong and believe that there is a moral structure to the universe, but how can you know God.

It is perplexing until you recognize that Christianity is a revealed religion. Christians believe that Holy Scripture is the Word of God; not just 'contains the word of God'. Without the Bible, we would know nothing of God, and certainly nothing of Jesus. Although Jesus is referred to by contemporary historians Pliny and Josephus, they tell us nothing about him. It is only the Bible that reveals him to us.

You sometimes hear it said, "My god is like ..." But only the God of the Bible is the real God, and the Bible tells us that if we want to know what God is like then we should look at Jesus.

There are many myths about the Bible and many challenges to its authenticity, but they are spurious. I shall produce evidence of this over the coming weeks, but if you take my advice you will save yourself the trouble. Just believe that the Bible, and you can take most modern translations rather having to learn Hebrew or Greek, just believe the Bible is the Word of God.

Drunken driving

About 100,000 British people are convicted every year of driving under the influence of alcohol. For men the numbers have stayed the same over the last 10 years, but for women the figures have increased by around 50%. However, there are still 8 men convicted for every woman.

Women have still a long way to go to be the equal of men.

Wednesday, January 09, 2008

God in the dock

In the Daily Telegraph today a columnist was making fun of Mike Huckabee. Apart from the fact that he is a Republican Candidate for the Presidential nomination I know nothing about him. However, he wears his religion on his sleeve, and this is something no British politician would dare to do. When Tony Blair was asked whether he prayed with George Bush, his minder replied, "We don't do God." Despite this Tony Blair was a devout man who has since followed Cardinal Newman to Rome.

Blair thought he would be a laughing stock if he spoke about his faith and the Telegraph columnist seeks to poke fun at Huckabee. The particular issue was a commercial in which the candidate wished everybody a 'magnificent Christmas'. Like many of his readers, I fail to find anything remotely amusing about the ad. But I would go further. I find it offensive that anyone should make fun of someone's sincerely held beliefs about God.

I am reminded of Psalm 2:

Why do the heathen rage, and the people imagine a vain thing? The kings of the earth set themselves, and the rulers take counsel together, against the LORD, and against his anointed, saying, Let us break their bands asunder, and cast away their cords from us. He that sitteth in the heavens shall laugh: the LORD shall have them in derision.

God does not need defenders; he can take care of himself. As CH Spurgeon said, "I would sooner defend a lion." But His people do need defending. I am sure Mike Huckabee can take care of himself, but believers whose faith is frail may cower beneath such cynicism. Christians should stand up for their brothers and sisters.

Monday, January 07, 2008

The forgotten father

Who are you trying to impress?

I have had it said to me in a derogatory manner; I expect you have too. When I was a child I was trying to impress my father. He was a severe man and not easily impressed. He always expected more. When he died in 1980 I was cast adrift. Who should I try to impress? Who was the arbiter of my performance?

Dad never lived to see me appear on television, become a professor, lecture to an audience of 5000, travel the world, become famous in my field. Most of my achievements came after he died. Who was I trying to impress?

In the Sermon on the Mount, Jesus wants us to impress out heavenly Father. I had never noticed it before but the reason we are to love our enemies is so that we may be 'sons of our Father in heaven'.

We are to do good secretly. If we boast about it we will have no reward from our Father in heaven. When we give to the needy we don't want to impress men but we should give secretly so that our Father, who sees what is done in secret, will reward us. When we pray we should go into our room and pray secretly, "Our Father...". Our Father knows what we need before we ask, so we don't need to babble - or pray eloquent prayers that impress the congregation. We should honestly and sincerely forgive others who offend us - because if we don't our Father will not forgive us. We should not make a show of our religion. It is the unseen Father who will reward us.

We should not be concerned by this world's goods or its rewards. If we are not careful they will master us. Our true Master has different priorities. And we can't serve two masters. In any case why worry about what we will eat and drink or what we will wear. Our Father knows our needs and will surely provide for them - and all that time wasted on worrying ...

Whatever we need, simply ask the Father. My father was austere, but he always provided for me. Will not my heavenly Father out-father my dad?

Sunday, January 06, 2008

God is love

Many years ago I had invited quite a famous broadcaster to speak at the local medical society. Over lunch we got talking about religion. "I can sum up my view of God in three words," he said, "God is love."

That is many people's view of God, but they couldn't say where it come from. It actually appears in chapter 4 of the first epistle of John, verse 8. The whole verse says "Whoever does not love does not know God, because God is love."

And the context is "Dear friends, let us love one another, for love comes from God. Everyone who loves has been born of God and knows God. Whoever does not love does not know God, because God is love. This is how God showed his love among us: He sent his one and only Son into the world that we might live through him. This is love: not that we loved God, but that he loved us and sent his Son as an atoning sacrifice for our sins. Dear friends, since God so loved us, we also ought to love one another. No one has ever seen God; but if we love one another, God lives in us and his love is made complete in us."

Taken by itself the three word answer can seem rather slushy, but in its context it reminds us of our need for a savior that was foreseen by God who made provision for our salvation even before we were aware of our need. It is a salvation that demands a response from us that we love one another, because it is only in this that God's love is made complete in us.

Secondary malignancies

An underlying genetic disorder is suggested for those cases myelodysplastic syndrome or acute leukemia that seem to have been caused by environmental toxins or exposure to cytotoxic drugs. The term “molecular epidemiology” was coined by Perera and Weinstein in 1982. It is defined as “the science that deals with the contribution of potential genetic and environmental risk factors identified at the molecular and biochemical level, to the etiology, distribution and control of disease in groups of relatives and in populations”. Polymorphisms of genes coding for proteins involved in DNA repair, DNA synthesis and drug and toxin metabolism have all been implicated in the causation of primary MDS and treatment-related MDS/AML.

Although decline in nucleotide excision repair, telomere maintenance and non-homologous end-joining leading to diminished stem cell functional capacity is a natural consequence of ageing It has been recently demonstrated that some patients with MDS have an inactivating Ser327Cys polymorphism in the gene coding for 8-oxoG DNA glycosylase (hOGG1), a key component of the base excision repair pathway. Other genetic polymorphisms that increase susceptibility to these diseases include the G/C variant at position 135 in the 5’ untranslated region of the RAD51 gene and the Thr241Met variant of the XRCC3 gene. Both genes are involved in DNA repair. These are but the latest examples of a huge area of research. Over 520 different amino acid substitution variants have been identified in the systematic screening of 91 human DNA repair genes for sequence variation. At least a third of these are classed as possibly or probably damaging.

The methylene tetrahydrofolate reductase (MTHFR) enzyme directs tetrahydrofolate towards methionine synthesis and away from dUMP synthesis, which is required for DNA synthesis and repair. Two MTHFR polymorphisms, C677T and A1298C, are associated with reduced enzyme activity. In a recent publication, both have been associated with the development of treatment-related MDS/AML.

Metabolism of cytotoxic drugs and potentially carcinogenic compounds is two-stage process. In phase I the substance is converted to its maximally mutagenic metabolite by cytochrome P450 enzymes. These enzymes are encoded by polymorphic genes. For example, the most abundant component of the cytochrome P450 system in human liver is CYP3A, which metabolizes etoposide, teniposide, cyclophosphamide, ifosphamide and the vinca alkyloids. A variant in the 5’ promoter region of the gene (CYP3A-V) diminishes production of the epipodophylotoxin catechol metabolite, which is a precursor of the DNA-damaging quinine. This variant is much less likely to be present in patients with treatment-related MDS/AML.

The phase I hepatic enzyme CYP2E1 metabolizes benzene to benzene oxide which spontaneously forms phenol and the same enzyme further metabolizes this to hydroquinone, a potent genotoxin. Detoxification of hydroquinone requires a phase II enzyme, nicotinamide adenine dinucleotide (P)H:quinine oxidoreductase (NQO1). Defects in the NQO1 pathway lead to accelerated telomere shortening and clonal hematopoiesis. The NQO1 polymorphism at codon 187 was studied by Naoe and his colleagues. The homozygous Ser/Ser genotype was significantly more common in treatment-related MDS/AML than in de novo AML or healthy individuals.

Anemic episodes preceding the development of acute leukemia after exposure to ionizing radiation were reported anecdotally in the early literature. Survivors of the atom bomb attacks in Japan exhibited features in their blood that would be today termed as MDS. It is now well established that secondary MDS occurs following bone marrow injury by alkylating agents and ionizing radiation. It is important to recognize that treatment with other cytotoxic and immunosuppressive agents may also lead to the development of MDS. The effect of the topoisomerase II inhibitors such as the epipodophyllotoxins and the anthracyclines and mitoxantrone in generating chromosomal translocations, particularly affecting the MLL gene at chromosomal band 11q23, are well known. Less familiar is the effect of antimetabolites such as 5-fluorouracil, azathioprine and fludarabine. Furthermore, the use of G-CSF for neutropenic support or to generate autologous stem cells for peripheral blood harvest has been implicated in the causation of secondary MDS.

The molecular epidemiology of MDS is extremely complex and we little understand how silent polymorphisms interact with unknown genotoxins to produce the disease. In the next decade we must expect that greater unraveling of this conundrum will lead us to both prevention and therapy.

Friday, January 04, 2008

The unchangeable nature of God

Does God change his mind?

There are several occasions where the King James version of the Bible says that God repented. In the NIV the word repented is avoided because God is unchanging in his purpose and intent, has complete foreknowledge and is not taken by surprise.

"He who is the Glory of Israel does not lie or change his mind; for he is not a man, that he should change his mind." I Sam 15:29

If you ever think that you are not good enough, that you need to try harder, that you have forfeited your salvation through lack of effort, do not despair. It is His purpose to bring believers into the full enjoyment of their promised inheritance. It is not His purpose for us to be constantly worrying about the future.

"Because God wanted to make the unchanging nature of his purpose very clear to the heirs of what was promised, he confirmed it with an oath. God did this so that, by two unchangeable things in which it is impossible for God to lie, we who have fled to take hold of the hope offered to us may be greatly encouraged. We have this hope as an anchor for the soul, firm and secure." Hebrews 6:17-19.

Thursday, January 03, 2008

I am weak but he is strong

The whole of Scripture could be summed up by. "Look at yourself; look at God." We have an opportunity to do just that in Mark 14:53-72.

First "Look at God"

Mark's version of the trial of Jesus is an abbreviated one. We do not the preliminary hearing before Annas, nor the appearance before Herod. The final meeting of the Sanhedrin is condensed to one verse (15:1). But the bones of the case was before Caiaphas, the real power among the Jews and this is what we have here.

There is first false testimony against Jesus. Just as today we get false testimony. Jesus is a freedom fighter. Jesus was one of the Essenes who married Mary Magdalene. Jesus was a magic mushroom. Just as then their testimonies do not agree.

Then there is misinterpretation of what he said. Did he say that he would destroy the Temple and rebuild it in three days? He certainly said something like that, but it is taken out of context. he was talking about his body which would be struck down then raised in three days. Just like today, we have JWs and Mormons and even Muslims quoting scripture at us, out of context and misinterpreted. And just as then their testimony does not agree.

Finally Caiaphas asks him "Are you the Christ, the Son of the Blessed One?"

Jesus answers, "I am."

Notice how Caiaphas says "Son of the Blessed one" to avoid using the name of God - I am that I am.

Jesus is not afraid, "I am," he replies. Then he quotes from Daniel 7:13 "one like a son of man, coming with the clouds of heaven" and Psalm 110:1 "The LORD says to my Lord: Sit at my right hand " with the implication of Daniel 7:14 " He was given authority, glory and sovereign power; all peoples, nations and men of every language worshiped him. His dominion is an everlasting dominion that will not pass away, and his kingdom is one that will never be destroyed."

Caiaphas might have fallen on his face to worship him, but he had other plans. He uses this statement to condemn him.

Look at Jesus and we see God in all his power and glory.

Look at ourselves.

In the second half of this passage we look at ourselves through Peter. Don't think that you would have done better. We are very prone to that. When we watch a dropped catch at baseball or a missed punt at football, we are prone to exclaim, "I could have done that!" But could we? Honestly? Peter was a giant among men. Think of his speech in Acts chapter 2. Could you have done that? Peter was a great leader of men. Would you like someone else to represent you?

Yet Peter denied Christ. Not once, but three times, and each time more vehemently. Finally when the slip of a girl accuses him, the big fisherman called down curses on himself and swore, "I don't know this man you are talking about!"

Then the cock crowed.

And Peter wept bitterly as he remembered - not his vain boasting - not his denials - but the words of Jesus.

Have you had a cock-crow moment? A moment when you realized you were in the wrong. The prodigal son's cock crowed when he found himself eating pigswill. Jonah's cock crowed in the belly of a great fish. For some it has found them drunk in a gutter. Others have found themselves splattered over a tabloid newspaper or locked in prison or bankrupted by debtors, or injured by drugs or diagnosed with AIDS.

Pray that it doesn't take any of these to bring you to your knees.

There is a legend that Peter wept every time thereafter that he heard a cock crow. I think it more likely that he praised God. For it is when we are brought low that we recognize our need of God and just as Peter was restored on the beach of Galilee, so the father is watching from the rooftops to welcome us, and when we are far off he will run to greet us and will throw his arms around us and put rings on our fingers and there will be angels rejoicing in heaven.

The grace of God is measureless and free.

The whole of the Gospel is looking at ourselves and seeing a sinner and looking at God and seeing a savior.

Secondary MDS and acute leukemia

As patients with CLL live longer they are experiencing a higher risk of secondary malignancy. The well known risk is of Richter's transformation in which an aggressive lymphoma supervenes. It seems that most cases are related to the immune defect that is present in CLL and that at least half are due to an inability to control the EB virus. However, it has come to light that patients who have autologous transplants have at least an 15% chance of developing MDS or AML. This is similar to what is found for patients with breast cancer and non-Hodgkin's lymphoma, and seems to be related to the chemotherapy used to induce remission or to condition the patient for the transplant. Moreover, patients treated with FCR or even plain fludarabine also have an increased risk of developing MDS or AML.

Why is it that some patients can receive this sort of chemotherapy safely and others are at risk of a second malignancy. The answer lies in the genes.

Despite the human genome having been sequenced, it is clear that everyone differs slightly from everyone else. These differences are due to polymorphisms. Some of us are blood group A, some B, some AB and some AB. We have different versions of a gene for blood groups. All differences between individuals have such an origin. Big ears, blue eyes, no ear lobes, red hair? All down to our genes. Some of these differences are due to a single amino-acid substitution in a protein. The best known is sickle cell disease. Here the substitution of a valine for a glutamic acid at position 6 in the beta chain of hemoglobin is sufficient to cause a crippling disease. However there are hundreds of similar substitutions in the hemoglobin molecule. Many of them cause no ill health whatsoever, but others cause various malfunctioning of the hemoglobin molecule.

Every other protein in the body is susceptible to the same sort of damage. I remember being astonished to discover when I was a junior doctor that the enzyme glucose-6-phosphate dehydrogenase has at least 160 different polymorphisms and that most don't cause a disease. In patients likely to develop MDS or AML after chemotherapy the polymorphisms mainly affect the enzymes concerned with DNA repair or toxin metabolism. Theoretically it should be possible to screen for these polymorphisms before administering cytotoxic drugs. We just need a little more time to be sure we fully understand all the mechanisms. I will write some moreabout the specific mechanisms as I study them, but here is something about gluthathione-S transferase:

A good example is the enzyme glutathione S-transferase (GST), which is involved in the detoxification of carcinogens such as alkylating agents and epoxides by catalyzing their conjugation to glutathione. It has been postulated that deficiency of this enzyme might be associated with a greater risk of MDS. Both GST M1 and GST T1 genes have a “null” variant allele in which the entire gene is absent. Chen et al found an odds ratio of 4.3 (95% CI, 2.5-7.4) for the GSTT1 null genotype and this was confirmed by Sasai et al who found that in individuals with the GSTT1 null genotype the odds ratio for disease risk were raised to 2.65 (95% CI 1.27-5.52) for de novo MDS, 4.62 (95% CI 1.48-14.4) in therapy related AML and 2.94 (95% CI 1.07-8.07) in AML with trilineage dysplasia.

On the other hand Davies et al found the GSTT1 null genotype similarly distributed in MDS patients as in a healthy population, but an odds ratio of 2.0 (95% CI, 1.3-3.1) for the GSTM1 null genotype in patients with AML/MDS compared with controls. Subsequently, three groups have demonstrated that the double null GSTT1/GSTM1 genotype to be overrepresented in Caucasian, Asian and Hispanic patients with primary and secondary MDS, AML and aplastic anemia.

Wednesday, January 02, 2008

Seek the Lord while he may be found.

I have just ordered some books from Amazon that deal with the question of militant atheism personified by Sam Harris and Richard Dawkins. Today I do not want to discuss "Did God make Man?" but "Why did God make Man?"

The answer is given in Paul's sermon on Mars Hill. where I stood early last year alongside the Acropolis. "God did this so that men would seek him and perhaps reach out for him and find him, though he is not far from each one of us." Acts 17:27.

This closeness of God to us is something we neglect at our peril. We are like the ostrich who buries its head in the sand. We imagine that because we cannot see God, he cannot see us. The prophet Jeremiah tells us, "I, the Lord, search the heart and examine the mind to reward a man according to his conduct according to what his deeds deserve." Jeremiah 17:10. In Psalm 139 David tells us that we cannot hide from God. We might think that in the vast universe we would be too insignificant to be noticed. We fail to recognize that space is silent. Our sins boom like a beacon across infinities of time and space.

Is there any hope? Jeremiah also tells us, "You will seek me and find me when you seek me with all your heart. I will be found by you ... and bring you back from captivity. " Jer 29:13-14.

Tuesday, January 01, 2008

Lines written on the first chapters of Genesis

Look at the sky, that vast expanse;
The mottled, dappled, mackerel sky;
The canopy for past romance
Where lovers wept their last goodbye.

Or burning blue, without a flaw,
So they, like we, might clearly feel
The scything sharpness of the Law;
Hard as a mirror cast in steel.

On other days to show His power
He made the lion and its prey,
But for the backdrop of this hour
He made the sky for one whole day.