Monday, November 29, 2010

Facing Goliath

After the coldest night in the UK for 25 years (-17 degrees Centigrade) I felt well enough to go to church yesterday morning. I wrapped up well, a wise choice because it was very cold in church. It was good to be there and to see my friends - it must be 7 weeks since I have been. The sermon was on David and Goliath and I found it very helpful.

This past week's symptoms have been increasingly difficult. They are mainly the effect of the irinotecan which causes colic and diarrhea. Buscopan is only partially helpful. The meeting with my oncologist was encouraging. I discussed with him whether treatment every two weeks was essential. He told me that quality of life was important and I could go to three-weekly if that meant I could more easily complete the 12 courses. I will certainly have a three week gap over Christmas, but I am contemplating having treatment on December 11th rather than the 4th.

Last week was a particularly bad week for side effects and they were beginning to get me down. At one point I found myself very angry at the whole situation. I know that anger is part of the experience of most patients with cancer, but I have always been able to approach my illness pretty rationally.

My angry thoughts were, "Why has this happened to me?" "What did I ever do to deserve this?" "It's not fair!" "Why does God let this happen to me?"

Yesterday's sermon certainly helped me.

Like Israel I was facing massive problems. Mine mightn't be nine feet tall like Goliath, but it seemed too big for me to tackle.

But whereas to the Israelite army Goliath seemed unfaceable, to David he was an uncircumcised Philistine defying God. David not only had a proper view of Goliath, he had a proper view of God: not a leader who had gone missing, but The LORD Almighty, the God of the armies of Israel.

David was also able to look at himself clearly. He knew that he had been anointed secretly by Samuel; he knew he had killed the bear and the lion when protecting his father's sheep; and he knew the hand of God in placing him precisely where he was to do the will of God.

Instead of complaining of our lot, we need to be aware that God is working his purposes out in us. If we were only given tasks that we could easily accomplish on our own, then we would easily claim the credit. But we are faced with tasks that overwhelm us and frighten us and come close to defeating us. Why? So that we realize that we need the Almighty Lord to accomplish them.

When we feel alone and deserted, then we need to turn to God - not blaming him for leaving us, but confessing that it is we who have stopped looking at him.

Psalm 10 begins: Why, LORD, do you stand far off? Why do you hide yourself in times of trouble?

But it ends: The LORD is King for ever and ever; the nations will perish from his land. You, LORD, hear the desire of the afflicted; you encourage them, and you listen to their cry, defending the fatherless and the oppressed, so that mere earthly mortals will never again strike terror.

The story of David and Goliath is well known. It was not the triumph of a littl'un over a big'un as it is popularly portrayed. It was the triumph over an upstart by the Almighty God who fights evil with good, lawlessness with justice, hate with love and haste with patience.

If there is a God, say some, let him wipe out poverty in Africa, sort out the cholera in Haiti, deal with the North Koreans, round up the drug-dealers, punish the pedophiles, stop the people trafficking, and rid the world of prostitution, pornography, murder, robbery, political corruption and fraud.

But God looks at robbers and murderers, prostitutes and pedophiles, drug dealers and even politicians and sees people who might be redeemed by the blood of his son, if they only had a second chance. So he waits.

Saturday, November 27, 2010

It's a busy life

Not much blogging this week. It has been the post-irenotecan week when I get a lot of intestinal colic which makes thinking difficult. I saw the oncologist on Friday and he gave me a good report. The CT scan was rather better than I had hoped with virtually all the disease except around the stricture disappearing. I get an extra week off over Christmas, but there are still 7 courses of chemotherapy to go.

I have spent the week advising on a medico-legal case that was very difficult to disentangle because the patient's hospital notes were lost, and have been missing for three years. It strikes me that if a hospital can't find notes after three years that they are not lost but hidden.

I have also been advising a marketing company on a marketing strategy for a drug in CLL. They didn't think much of my suggestion that it should be given away free until it has been shown to cure anyone.

Anyway I hope the next week will be easier to cope with.

What to do about our prisons?

Ken Clarke, The Lord Chancellor, wants to close down three prisons. This is in contrast to the last administration which had a program of building more prisons and bigger ones. We already lock up more people every year than any other country in Western Europe, but far less than they do in America. What is the right approach?

There seems little argument that many people in prison are there because they are inadequate, addicts or mentally ill. Clearly these people should not be there. It is also probably true that there are a lot of people out there walking free who ought to be in prison and who are not. The arrest and imprisonment of one family in Nottingham cut burglary in that city by 50%. If only the evidence had been there before, much crime could have been prevented.

What is prison for? A murderer has recently won a court case on the basis of the European Court of Justice ruling that a blanket ban on prisoners voting in National Elections is unjust. Prison Reform agencies often say that the deprivation of liberty is the sole punishment of imprisonment and that there should be no other deprivation. Outsiders moan that prisoners lounge around all day watching television, playing games and having conjugal visits.

I think the problem is the idea that prison should be one-size-fits-all.

It is said that many in prison are themselves victims of crime. I know a young man who was in prison for two weeks last year. His offence was driving without a valid driving licence. He is a plumber who was burgled and lost £30,000 from his safe. The £30,000 in cash was there because he avoided VAT by doing jobs for cash – a not uncommon practice among artisans. He thought he knew the thief, but in view of his dodgy business practices he did not tell the police. He was uninsured and had to declare bankruptcy. In his despair he took to drink and lost his licence for drink-driving. He had to employ a driver to take him to his plumbing jobs, but for one late-night call-out he took a chance and drove himself. The police were waiting for him are stopped him.

Prison for him was a short sharp shock. It was an open prison with a very easy regime. He has an addictive personality. Instead of alcohol, he concentrated on exercise. By spending most of his day in the gym he lost a lot of weight and got very fit. When they let him out he continued the exercising and began to sort his life out. Subsequently he has had a few drinking binges, which have seemed like setbacks, but he has learned that he is an alcoholic and must never drink again. He has had one relationship with a bright young teacher with a small child, but it came to grief when he got drunk. Currently he seems to be doing well. He is working and supporting himself and exercising.

Did prison help? I think it probably did. The shame and shock of it turned out to be a corrective for him. It doesn't just stop there and he still has a problem, but I think he is winning.

So what is my recipe for prisons?

First, there are people who are not safe to be walking around, whose liberty must be curtailed for the safety of the rest of us. Here I would include violent psychopaths, dangerous pedophiles and I would add seditious terrorists. If there is no chance of changing these people then society cannot contain them. Of course, we should be researching how to treat these people, but treatment alternatives are not promising. Violent schizophrenics are a minority and can generally be controlled by a 'chemical cosh' - strong anti-psychotic drugs that control the symptoms. However, many schizophrenics cannot bear the suppression of mental energy that this involves and default on their medication. They are mostly voluntary patients, but if they default they may become killers - more often suicides than murderers - and this is a difficult problem for the authorities. Once they become compulsory patients, then depot neuroleptics may be enforced; the alternative is a long-stay secure mental hospital.

Sociopaths are different. No-one knows what is wrong with their brains. They seem to be unable to understand what it means to live in a society, where give and take is necessary for living. Click here for a description of what a sociopath is like. Here are some of the characteristics: They never recognize the rights of others and see their self-serving behaviors as permissible. They appear to be charming, yet are covertly hostile and domineering, seeing their victim as merely an instrument to be used. They may dominate and humiliate their victims. They have no problem in lying coolly and easily, and it is almost impossible for them to be truthful on a consistent basis. They may have a deep seated rage at their core. They do not see others around them as people, but only as targets and opportunities. Instead of friends, they have victims and accomplices who end up as victims. The end always justifies the means and they let nothing stand in their way. Joy, love and compassion are more likely to be feigned than experienced and serve an ulterior motive. They are outraged by insignificant matters, yet remain unmoved and cold by what would upset a normal person. Since they are not genuine, neither are their promises. They are unable to empathize with the pain of their victims, having only contempt for others' feelings of distress and readily taking advantage of them. Promiscuity, child sexual abuse, rape and sexual acting out of all sorts are characteristic.

It is estimated that 3% of men and 1% of women are sociopaths. Obviously, we cannot lock them all up. Many of them have had such a crafty way of life that they appear normal to outsiders, but those who live with them know them as manipulating bullies who make their lives a misery. Because they go undetected, they wreak havoc on their family; on people they work with, and on anyone who tries to be their friend. A sociopath deceives, takes what he (or she) wants, and hurts people without any remorse. Sociopaths don't feel guilty. They don't feel sorry for what they've done. They go through life taking what they want and giving nothing back. They manipulate and deceive and convincingly lie without the slightest second thought. They leave a path of confusion and upset in their wake.

Researchers have found that the brains of sociopaths function differently to normal people. Their brains function in a way that makes their emotional life irredeemably shallow and yet they are capable of mimicking emotions like professional actors.

There is no known cure or therapy for sociopathy. In fact, some evidence suggests that therapy makes them worse because they use it to learn more about human vulnerabilities they can then exploit. They learn how to manipulate better and they learn better excuses that others will believe. They don't usually seek therapy, unless there is something to gain from it.

Given all that, there is only one solution for dealing with a sociopath: get him or her completely out of your life for good. This seems radical, and of course, you want to be fairly sure your diagnosis is correct, but you need to protect yourself from the drain on your time, attention, money, and good attitude. Healing or helping a sociopath is a pointless waste of your life.

For those sociopaths who commit serious crime, prison has a place - not for rehabilitation, it won't work - not for retribution; it is like water off a duck's back - but for safety's sake. Violence, murder, robbery and rape will just recur if there is an opportunity. For these people life must mean life and for them deprivation of liberty is the purpose of prison.

A good example might be the young man who stabbed Phillip Lawrence. Learco Chindamo's brutal gang 'Venom' which terrorised North London in the mid-1990s. In 1995 Chindamo stabbed headteacher Philip Lawrence to death when he came to the aid of a pupil at the school gates. After serving 14 years Chindamo claimed to be reformed but he has been re-arrested found guilty of mugging a man at and ATM machine in Camden while on a weekend release. In my opinion Chindamo should be behind bars for the rest of his life.

The offences of sedition and seditious libel were abolished by the last Labor government in 2009. It was replaced by hate crimes legislation. The prime purpose of the Act was to protect Muslims and homosexuals from so-called hate crimes while continuing to support free speech. I think the Act was one of the reasons that Labor was defeated at the election. In fact their attempt to get the Bill through unscathed was defeated in the House of Lords, where the Waddington Amendment was passed: In this, for the avoidance of doubt, the discussion or criticism of sexual conduct or practices or the urging of persons to refrain from or modify such conduct or practices shall not be taken of itself to be threatening or intended to stir up hatred. However, it is not clear whether what would have been called sedition or treason is sufficiently guarded against by current legislation. In law, sedition was, I quote, overt conduct, such as speech and organization that is deemed by the legal authority to tend toward insurrection against the established order. Sedition often includes subversion of a constitution and incitement of discontent (or resistance) to lawful authority. Sedition may include any commotion, though not aimed at direct and open violence against the laws.

The difference between sedition and treason consists primarily in the subjective ultimate object of the violation to the public peace. Sedition does not consist of levying war against a government nor of adhering to its enemies, giving enemies aid, and giving enemies comfort. Nor does it consist, in most representative democracies, of peaceful protest against a government, nor of attempting to change the government by democratic means (such as direct democracy or constitutional convention).

Sedition is the stirring up of rebellion against the government in power. Treason is the violation of allegiance to one's sovereign or state, giving aid to enemies, or levying war against one's state. Sedition is encouraging one's fellow citizens to rebel against their state, whereas treason is actually betraying one's country by aiding and abetting another state. Sedition laws somewhat equate to terrorism and public order laws.

I am no lawyer and I cannot judge what wording laws ought to have, but I can see offences that need to be remedied. For example, British citizens or British Residents, who train or fund the training of young men to fight against British soldiers in a war zone, or who volunteer to fight or actually fight, should not be able to claim the privileges of living here. They should either return to their country of origin or be subject to a law that results in their being imprisoned. They should remain in prison unless their view changes or until the conflict ends. There needs to be a limit on free speech - the so called Shouting "Fire!" in a Theater” limit. Speech so inflammatory as to possibly lead to violence, damage or injury should not be allowed.

Framing such legislation is bedevilled by the European Human Rights Act, which Labor incorporated into English law, but it really should be possible to protect our society against terrorists.

Turning now to lesser crimes. Much petty theft is to feed the habits of drug addicts. There is little point in putting these people in prison, where incidentally they seem to be able to get hold of drugs. I firmly believe that abstinence is the only way to get addicts off drugs. Methadone is a hopeless cause. Decriminalizing is stupid. Most addicts would rather be off if possible; it just doesn't seem possible. Then again, addicts have an addictive personality and need to get addicted to something less damaging. Whether it is exercise, yoga, mountain climbing, religion, work, AA, or property developing probably doesn't matter. Diversion therapy is better than talking therapy, antidepressants or cognitive behavioral therapy and certainly better than prison. I happen to think that psychiatry has taken a wrong turn. Antidepressants seem to be mainly placebos and the Freudian type of digging up the past just makes people relive their pain. Many doctors I know believe in distraction therapy – you just have to get on with your life.

I am told that there are 370,000 heroin addicts in the UK and that 285,000 are on a methadone program. Methadone, I am told, doesn’t give you a high but medicates the withdrawal symptoms. In any case only 3% of people on methadone come off drugs completely. Cold turkey with proper support works better.

What about financial crimes? These should be dealt with by repaying the money and a fine equal to half the amount stolen. This may involve confiscation of assets and imprisonment if the money can’t be found. In prison they should work until the money and fine is repaid.

Is there any place for rehabilitation? Perhaps there is for younger criminals. They might get three attempts at it then incarceration until too decrepit to do their crimes. Prisons have been too much Universities of Crime, so freshers should be separated from sophomores and sophomores from final year students. Graduates are in for good.

What about education? Too many in prison are illiterate and innumerate. This is a condemnation of our educations system. Clearly this should be remedied before they go to prison, but perhaps young men can be rescued after the offence and before incarceration. There used to be Reform Schools. I guess they were thought too brutal.

Tuesday, November 23, 2010


MDS is the myelodysplastic syndrome. It is common in the elderly - probably commoner than CLL. It shows it self as low levels of Hb, platelets and neutrophils. The hallmark for diagnosis is the presence of particular abnormalities in the bone marrow that takes a highly skilled hematopathologist to spot. Many cases are missed.

It is more common than expected in patients who also have a lymphoid tumor and as long ago as 1974 people were making the diagnosis of CLL and MDS simultaneously before any treatment was given.

The outcome of MDS is variable: about a third turn into AML, about a third die because they get infections because they have low neutrophil counts or bleed because of their low platelet counts and about a third die from an unrelated condition never having needed treatment for their MDS.

Therapy-related MDS has a worse prognosis than that - largely because therapy causes chromosomal abnormalities (monosomy 7 and monosomy 5) that are associated with poor prognosis. Alkylating agents are most responsible for therapy-related MDS - Mustine, Melphalan, Busulphan, Treosulfan, Theotepa, Bendamustine, Cyclophosphamide and Chlorambucil - have all been implicated.

Actually, in CLL there have been very few reports of treatment-related MDS/AML compared to say, Hodgkin's disease. In an early French trial which gave low-dose continuous chlorambucil there were a few excess cases, but the same group found no problem when they switched to intermittent chlorambucil. In the original Kanti Rai trial that compared fludarabine (F) with fludarabine+chlorambucil (FChl) with chlorambucil (Chl) alone, there were 6 cases of late MDS, 5 in the FChl arm and one in the F arm. there were none in those who only had chlorambucil.

My own experience with therapy-related MDS was mainly in patients treated with cyclophosphamide - I once had a fairly large autoimmune practice and had lots of patients treated with pulse cyclophosphamide. I also saw it after low dose chlorambucil for ovarian cancer, after treosulfan for ovarian cancer, after MOPP treatment for Hodgkin's disease, but never after chlorambucil alone treatment for CLL.

We also saw cases of therapy-related MDS in patients treated with fludarabine alone or with those who had fludarabine after an alkylating agent. Others have reported MDS after autograft when a fludarabine induction or conditioning regimen was used. So can fludarabine cause therapy related MDS. From our experience of other similar drugs (those with substitute purine or pirimidine bases) we would not expect it to, but fludarabine has a profound effect of the regulatory T cells and one can envision a role here. One of the roles of regulatory T cells is to suppress small malignant clones that may arise from DNA damage. Without this role, one can imagine these errant clones expanding and replacing the normal marrow.

So does this happen with FCR? It may be too early to tell. So far there have been no reports in teh German CLL8 trial of this happening.

Parallel to the CLL8 trial which was for untreated patients, Roche ran a similar trial for previously treated patients. I was chairman of the Data Monitoring Panel for that trial, and we were struck by the occurrence of neutropenia in these patients. These events have now been published so I guess that there is no harm in relating our concern. Neutropenia was sometimes prolonged after the treatment finished, and sometimes recurred some months after it had recovered. I was very concerned that this might be secondary MDS and convinced Roche that bone marrows should be sent out to expert reviewers to look for it. This they did and amongst those who reviewed the marrows was Barbara Bain, perhaps the leading hematopathologist in the world. She could find no evidence of MDS.

I believe that the long standing neutopenia following rituximab is nothing to do with MDS, but involves the sequestering of neutrophils in the spleen and elsewhere, because of the fact that neutrophils have Fc receptors that bind to immunoglobulin. I am not sure of the precise mechanism and more work needs to be done. Characteristically such patients respond poorly to Neupogen. I would certainly like to see more research done in this area.

Thursday, November 18, 2010

Disordered Minds

Minette Walters lives here in Dorset and is one of the top crime writers. I have just read 'Disordered Minds' which is set in Bournemouth, though not a Bournemouth that I recognize. It is what you would call a psychological thriller.

Gregory House says, "Everybody lies." He is right, but in this book everyone creates a new personality for themselves. People construct a persona that makes them comfortable with themselves, even though everybody else sees through it. This makes for a fascinating read as the threads unravel and the truth is gradually revealed. The main investigator is not who he claims to be, not is the murderer. The person convicted didn't do it and one person can't remember doing it. The guilty accuse the innocent and the innocent protect the guilty, though how innocent are the innocent.

If you haven't already, read it.

another health update

I went into the hospital today fro a further check prior to my next chemotherapy on Saturday. They had the CT result, which has shown a 20% reduction in size of the tumor after 4 courses. Although this does not sound much, the tumor is in a hollow tube, so we are talking about its external diameter. Since the tube seems to have started working I think I can assume that the internal diameter is larger so the thickened wall is less. Smaller peritoneal thickenings are also less on the scan, so all in all a good result. I am certainly feeling better.

The oncologist agreed with my hypothesis.

Wednesday, November 17, 2010

health report

Since the weekend, my health has improved considerably.

I've been quite ill following the last chemotherapy. Foolishly perhaps, I decided to stop taking steroids after the last course because I was losing power in my legs. Anyway, I got septicemia with rigors and drenching sweats and had to go on antibiotics. Following this I had terrible colicky pain until I restarted the steroids and since then I have been gradually recovering and have suddenly put on 7 pounds in weight.

In retrospect I think that what is happening is that the chemotherapy is working. I had the operation in June for a stricture where the cancer had recurred and the lesion was by-passed, taking a few feet of bowel out of functional activity. I could feel a lump around where the appendix ought to be. Since starting the chemotherapy the lump has gone. I think that the stricture has been relieved. The colicky pain was caused by bowel contents trying to force themselves through the original pathway, but until I restarted the steroids, which reduce the swelling and edema, the passage was too narrow. Afterwards the passage opened up and suddenly I had a greater absorptive surface - hence the weight gain. I had been eating chocolate and lots of cheese, drinking full cream milk and banana milk shakes in an effort to keep my weight up, but suddenly all that fat was being absorbed. I had a CT scan today so next week I will be able to judge whether my hypothesis is correct.

A del 13q anomaly explained

After Carlo Croce stressed the importance of the miR-15 and 16 genes in del 13q14 CLL we had a bit of problem because the smallest minimally deleted region (MDR) that we had found in Bournemouth excluded those genes. Many deletions did include them, but a significant number did not. Now an explanation is available . The paper is part of the collaboration between Bournemouth and the Karolinska. One of our stars, Martin Corcoran has gone to work in Stockholm to carry on this endeavor.

It turns out that the Leu2 gene, which is in the MDR of 13q14 acts as a promoter gene for miR-15a and miR-16-1, so that if it is deleted they are down regulated. In several cases they were able to show that miR-15a and miR-16-1 were intact, but non-functional because the Leu2 gene was deleted. Although the miR genes have been shown to have an effect on bcl-2, it appears that the more important effect is on the G1 Cyclins E1 and D1. Leu2 negatively regulates these oncoproteins through the effects of miR-15a and miR-16-1. This deletion of either Leu2 or the miR genes will allow cell proliferation to increase because the G Cyclins have lost their braking system.

Further information that comes from this paper demonstrates that Leu2 is negatively regulated by the Myc oncoprotein, which is activated in many hematological malignancies and might be involved in some cases of Richter's transformation.

Movies - Boomerang (not Eddie Murphy) one to look out for.

Courtesy of Film 4 I watched an early (1947) Elia Kazan film called Boomerang. It had a stellar cast including Dana Andrews, Jane Wyatt, Arthur Kennedy, Ed Begley, Lee J. Cobb, Karl Malden, and Sam Levene.

Based on a true story and filmed on location in a documentary style, I thought it just great. It had one Oscar nomination for best screenplay, but how much better it was than most of the stuff we get served up today. No sex, no swearing, no innuendo, a soundtrack that let you hear every word, no intrusive music; the black and white photography was sharp and the story was important.

It showed the danger of trying to get a confession by torture. This was just sleep deprivation, not brutality. Sleep deprivation was supposed to have been introduced by the Chinese in the Korean war, but clearly was being used in New England police stations before that. It showed the unreliability of eye-witness evidence and the danger of newspaper headlines in putting pressure on politicians. It showed the risks of public officials being subject to local elections and that even those elected on a whiter-than-white platform are corruptible.

Without Film 4 I would have had to pay £42 to buy the DVD! Thank you Film on 4.

Del 13q14 - the Bournemouth background

I feel a sort of ownership for del 13q14, since it was on some of my patients that the first cases in both CLL and myeloma that it was discovered in 1987. The paper was a collaboration between my colleague David Oscier and Marina Seabright,in nearby Salisbury, who had discovered Trypsin banding of chromosomes, a discovery that opened up the localization of genes on chromosomes. David went on to do a great deal of work on del 13q14 in CLL, including showing that it had a good prognosis and that most cases had mutated IGVH genes .

At first we thought it must be related to a tumor suppressor gene – there was already a known tumor suppressor, Rb1, at 13q12. So David set about finding the minimally deleted region on 13q14 and sequencing the genes that could be found there. Unfortunately, the link with the Salisbury lab was broken at the time as Marina Seabright retired, and her successor, though an esteemed scientist and FRS had little or no interest in leukemia and transferred the research funds to a pet project of her own involving the fragile X chromosome. She was within her rights to do this but it disappointed us. Luckily I was able to find internal money from my own budget and employ three experienced cytogeneticists from Salisbury so that we could establish our own chromosome lab in Bournemouth. Since this move has generated over 60 publications we can’t say it was regrettable, but we are pleased to say that now Nick Cross has been appointed to Salisbury, the link has been re-established and had has been very profitable to science.

New collaborations were set up with the Karolinska in Stockholm and with the Vavilov Institute of General Genetics, Moscow. It was strange that David had to go abroad to establish these collaborations, but I seem to remember an attempt to set up a British collaboration, where the potential collaborator’s view of ‘collaboration’ was more akin to ‘commandeering’ and that attempt was abortive.

By 1998 these collaborations had produced a molecular map of the minimally deleted area and had identified three genes, Leu1, Leu2, and Leu5 within the minimally deleted area. None of these genes were translated as protein and none seemed to be tumor suppressor genes. If you remember this was the time of all the razzmatazz about the Human Genome Project when the big surprise was how few genes there seemed to be controlling our bodies – nearer to 30,000 than the expected 100,000. So the search turned to genes that controlled expression of protein rather than those that translated it.

This was where the big boys stepped in. There was sufficient interest in this subject and by 2001 both Columbia New York and Philadelphia had re-sequenced the minimally deleted area and confirmed our work. Then in 2002 Carlo Croce and George Calin discovered the missing miR genes on the deleted site and suggested that these were allowing an over expression of bcl-2, a known problem in CLL.

I quote from their paper, “Micro-RNAs (miR genes) are a large family of highly conserved noncoding genes thought to be involved in temporal and tissue-specific gene regulation. MiRs are transcribed as short hairpin precursors (≈70 nt) and are processed into active 21- to 22-nt RNAs by Dicer, a ribonuclease that recognizes target mRNAs via base-pairing interactions.”

It all seemed settled here, but then it all got more complex as it became clear that del 13q14 didn’t mean that everything in the garden was rosy for everybody. Some of the problems were straightforward. We had always said that it was only isolated del 13q14 that had the favorable prognosis; any accompanying abnormality trumped it. We had also made it clear that having unmutated IGVH genes called the whole party off; they also trumped it. Our own careful studies had also revealed that del 13q14 was much commoner than had been published; most studies had suggested that up to 50% of CLL cases had the missing section, but when we looked carefully we found that there were translocations that had lost a small porting of 13q and other very small interstitial deletions that had lost small parts of the critical region. It was clear that some part of 13q was involved in CLL in over 80% of cases.

Then there were clinical questions. What about when both chromosome 13s had lost parts? One paper suggested that this carried a worse prognosis, but our own data did not support this. Were there any differences if a large part of the chromosome was missing compared with a small part?

Thankfully, answers are beginning to emerge, and there are papers at ASH this year that address the problem.

I think that that is all I am going to write today. I shall bring you all an update in a short while to explain how things are now.

Tuesday, November 16, 2010

George Mathe

George Mathe has died at the age of 88. He was a pioneer of bone marrow transplantation and immunotherapy. He is chiefly famous for his failures. His first transplants were for accidental radiation overdoses and they all died. He discovered graft versus host disease as a consequences. He later introduced BCG as an immune adjuvant to treat acute leukemia. He insisted that it worked when it didn't. He even suggested that those who could not repeat his work were using the wrong BCG - an argument reminiscent of those who criticised smallpox vaccination by suggesting that those who could not reproduce Jenner's work were using the wrong kind of cow.

I only met him the once, in a restaurant in Italy. I found him bombastic and opinionated. He was a bright guy who was lauded in France and had early fame for his courage and innovation, but his contribution to the field was more talked about than real and I don't think he deserved a share in the Nobel Prize that Don Thomas won. Can't say that I liked him much.

Monday, November 15, 2010

Remembrance Day 11th November 2010

One thing the British do well is ceremony. On Saturday night I watched on television the Service of remembrance from the Albert Hall. This is the most solemn day in the British calender when on the anniversary of the armistice in the First World War, we remember our war dead in that and subsequent conflicts. It is especially poignant when our troops are engaged in daily battles as they are in Afghanistan.

The symbol of it all is the poppy, which grew in the fields of Flanders where the great battles of the Somme, and Ypres were fought. Everyone wears a paper poppy on their coat. David Cameron recently almost offended the Chinese on his recent visit there. They thought it was a reference back to the Opium Wars.

The actual service was splendid. The whole Royal Family was there and all leading politicians, but also thousands of ordinary people as well as serving soldiers. Near the end there was two minutes silence during which thousands of paper poppies fluttered down from the soaring ceiling.

I was pleased to see that one of the hymns was How Great Thou Art!

O Lord my God! When I in awesome wonder
Consider all the works thy hand hath made,
I see the stars, I hear the mighty thunder,
Thy power throughout the universe displayed;
Then sings my soul, my Saviour God, to Thee,
How great Thou art, how great Thou art!
Then sings my soul, my Saviour God, to Thee,
How great Thou art, how great Thou art!

And when I think that God his son not sparing,
Sent him to die - I scarce can take it in,
That on the cross my burden gladly bearing,
He bled and died to take away my sin:
Then sings my soul, my Saviour God, to Thee,
How great Thou art, how great Thou art!
Then sings my soul, my Saviour God, to Thee,
How great Thou art, how great Thou art!

When Christ shall come with shout of acclamation
And take me home- what joy shall fill my heart!
Then I shall bow in humble adoration
And there proclaim, my God, how great thou art!
Then sings my soul, my Saviour God, to Thee,
How great Thou art, how great Thou art!
Then sings my soul, my Saviour God, to Thee,
How great Thou art, how great Thou art!

There was the Duke of Edinburgh straight like a ramrod singing out the words for all he was worth and the Queen, jiggling slightly to the rhythm like a Momma in a Gospel church. And there were Ed Milliband the Labour leader and Nick Clegg the Liberal Democrat leader, both avowed atheists, singing out the second and third verses as if they believed them.

What is the world coming to?


The topic of torture has come up again because George W Bush is doing the bookselling round, pushing his memoirs. He still believes that waterboarding is not torture and that it was justifiable to use waterboarding to extract information from terrorists. He also stated that the intelligence that led to the discovery of the 'liquid bombs' destined to be loaded on airplanes at Heathrow came from waterboarding evidence

Torture has come up twice recently on "Question Time", the BBC program on which a panel of politicians, businessmen and celebrities are asked difficult questions from the audience. The politicians are always against torture and waterboarding is regarded as torture.

Kiefer Sutherland has established his reputation with the series '24' in which numerous ticking bomb scenarios are explored with a view to justifying torture in that situation. The politicians of Question Time disregard such an argument saying that these situations don't happen in real life; they are a fiction writer's invention.

Interestingly, the businessmen on the panels have felt that the arms of the security service should not be tied. The weapon of torture should be held in reserve for the extreme case. At least it would leave a hint of fear in the mind of the criminal.

In fact waterboarding is used in the UK. It is part of the training of the SAS and SBS so that they have experience of resisting interrogation if they are captured. However, it has been the policy of successive British governments that we do not torture prisoners. This has dated from the Northern Ireland ‘Troubles’ when it was held that even insisting that a prisoner stand in a particular position so that lactic acid accumulated in his muscles and caused painful (though physically unmarked) legs amounted to torture and was illegal.

In America it is widely assumed that the United States tortured senior Al Qaeda leader Khalid Shaikh Mohammad. There is irrefutable evidence that it tortured large numbers of Iraqi prisoners and there is strong evidence that it tortured prisoners at Guantanamo Bay prison in Cuba, where suspected Al Qaeda terrorists are held.

Mirko Bagaric is a Professor Law and Head of the Deakin Law School. He believes that the belief that torture is always wrong is misguided and symptomatic of the alarmist and reflexive responses typically emanating from social commentators. He thinks that this is undesirable and should be corrected; that this type of absolutist and shallow rhetoric lies at the core of many distorted moral judgments and that Americans as a community continue to sustain an enormous amount of injustice and suffering in their society and far beyond their borders because of this attitude.

He gives this as an example where all the warm and fuzzy principles would go out of the window: A terrorist network has activated a large bomb on one of hundreds of commercial planes carrying over three hundred passengers that is flying somewhere in the world at any point in time. The bomb is set to explode in 30 minutes. The leader of the terrorist organization announces this via a statement on the Internet. He states that the bomb was planted by one of his colleagues at one of the major airports in the world in the past few hours. No details are provided regarding the location of the plane where the bomb is located. Unbeknown to him, he was under police surveillance and is immediately apprehended by police. The terrorist leader refuses to answer any questions to police, declaring that the passengers must die and will shortly.

Mirko Bagaric goes on to argue: Who in the world would deny that all possible means should be used to extract the details of the plane and the location of the bomb? The answer is very few. Claims that there is an absolute proscription against torture would run very hollow. The passengers, their relatives and friends and society in general would expect that all means should be used to extract the information, even if the pain and suffering imposed on the terrorist resulted in his annihilation. Given this, it is illogical to insist on a blanket prohibition against torture. The debate must turn to the circumstances when torture is morally appropriate. The reason that torture in such a case is defensible and necessary is because the justification manifests from the closest thing we have to inviolable right: the right to self defense, which of course extends to the defense of another. Given the choice between inflicting a relatively small level of harm on a wrongdoer and saving an innocent person, it is verging on moral indecency to prefer the interests of the wrongdoing.

An example, not involving torture has surfaced close to home here. A man who lived not far from here was looking after his wife with dementia. Eventually her state deteriorated to such an extent that he could not cope and his own quality of life was deteriorating. It became necessary for her to be cared for in a nursing home. Unfortunately he would not recognize the fact and his own mental state was deteriorating. When the ambulance came to collect her he confronted the paramedics with his illegally held service revolver and fired warning shots. The paramedics called the police who sent an armed response unit and a hostage negotiator.

In the UK we are rightly proud that are police are not armed. Homicides are still relatively rare in the UK and are largely confined to family disputes or black-on-black gang warfare in big cities. There is a highly trained armed response unit attached to the police, yet for every 100 times they are called out they discharge their weapons fewer than 5 times. This was one of the occasions. After some time of negotiation, the old man fired his revolver and hit a policeman in the chest. Another policeman fired back and killed the man. The first policeman was wearing body armor which stopped the bullet and all he suffered was nasty bruising, but it could have been a head shot. I think that most people would agree that when a policeman has been hit by a bullet, his colleagues are permitted to fire back and the old Cowboy and Indian story of just ‘winging’ the culprit has long been shown up as a fairy story. Lethal force has to be applied.

In another recent incident, a London lawyer, high on booze and drugs was seen brandishing a shotgun from the window of his apartment while shouting and threatening both suicide and mayhem. Despite negotiations his behavior continued unchecked and when he fired his shotgun indiscriminately at the waiting crowd he was killed by a police marksman.

It is always a matter of judgment when to fire, but the guiding principle is self defense and the defense of the innocent.

Bagaric continues: The analogy with self-defense is further sharpened by considering the paradigm hostage taking scenario, where a wrongdoer takes a hostage and points a gun to the hostage’s head threatening to kill the hostage unless a certain (unreasonable) demand is met. In such a case it is not only permissible, but desirable for police to shoot (and kill) the wrongdoer if they can get a ‘clear shot’. This is especially the case if it is known that the wrongdoer has a history of serious violence – and hence is more likely to carry out the threat.

There is no logical or moral difference between this scenario and one where there is overwhelming evidence that a wrongdoer has kidnapped an innocent person and informs police that the victim will suffocate or be decapitated by a co-offender if certain demands are not met. In the first scenario, it is universally accepted that it is permissible to violate the right to life of the aggressor to save an innocent person. How can it be wrong to violate an even less important right (the right to physical integrity) by torturing the aggressor in order to save an innocent life in the second scenario? The scenarios are morally equivalent.

Torture is permissible where the evidence suggests that this is the only means, due to immediacy of the situation, to save the life of an innocent agent. What level of harm can be inflicted to save the innocent person? As with self-defense, lethal force is justifiable. This is the only situation (torture as self defense) where it is justifiable. Thus of course we do not condone any of the recent claims of torture which were apparently undertaken as punitive measures or in a bid to acquire information where there was no evidence of an immediate risk to the life of an innocent person.

The problem with these examples is, as the Question Time panelists realized is that they never (or hardly ever) happen in real life. They would argue that torture is so morally repugnant that there must be an absolute ban on its use and that society must accept that bad things happen that we can’t do anything about. We all realize that you can’t trust a confession obtained by torture – remember the trial of Anne Boleyn - but information obtained by torture may or may not be true and the information is testable. The recent printer bomb sent from Yemen and discovered at East Midlands airport would have exploded less than three hours after it was removed from the airplane. The information about this bomb was obtained from Saudi Intelligence. We have no idea whether torture was used, but it is widely believed that that organization has not the same sensitivities about its use. Had the information not been available that plane and its crew would have been lost short of the American coast.

Bagaric continues: The examples above are hypothetical but the force of the argument cannot be dismissed on that basis. Fantastic examples play an important role in the evaluation of moral principles and theories since they sharpen the contrasts between them and illuminate the logical conclusions of the respective principles and in this way test the true strength of our commitment to the principles. Moreover, given the extreme measure that some disgruntled groups around the world are now taking to advance their causes, it is not difficult to envisage the community being faced with such a reality. We should be prepared for that and appoint a small number of officials who are competent to issue ‘torture warrants’ to police.

He advances a real life case that might have been worthy of torturing the perpetrator. In June 2006 Joseph Korp and his lover knocked his wife on the head and locked her in the boot of his car and left her to die. Had the police apprehended them, would they have been justified in torturing them in order to find the wife’s whereabouts before she eventually died? And what better way of torturing the one by inflicting damage on the other. You wouldn’t even need to do it, just a threat and some screams night work the oracle. In the end the wife was found alive, but died in hospital without regaining consciousness

Of course there are arguments against Bagaric’s approach. The first is the slippery slope. Start allowing torture in extreme circumstances and soon it will be used in less extreme. Is this likely? Internationally torture is widely used. Amnesty International has recently reported that they had received, during 2003, reports of torture and ill-treatment from 132 countries, including the United States, Canada, Japan, France, Italy, Spain and Germany. Perhaps, like smoking cannabis an unrealistic total ban has driven it underground. perhaps legislation allowing some kind of coercive questioning in highly regulated circumstances would actually lessen the amount of torture happening.

The second argument is that it would ‘dehumanize’ society as a whole. But would it? Does our tolerance towards self-defense dehumanize us? Perhaps if we favored the interests of the innocent over wrongdoers society would be more humanized?

The third argument is that we could never be totally sure that torturing a person would in fact result in us saving an innocent life. But it is the same as with shooting in self defense. In the ‘Death on the Rock’ story where it was believed that two IRA terrorists were about to blow up a car bomb and they were shot by undercover British agents, it was still to shoot. Decisions must be based on the best evidence at the time, otherwise we would never leave our houses – we might get a hit by a car on the way to work.

Having read Bagaric, and watched all the episodes of ‘24’ I think his arguments have a certain force. I think it is facile to simply brush torture away as if we lived in a perfect world; as if we were simply nice towards bad people they would be nice back to us. We live in a wicked world and nasty people have to be controlled. Sometimes we need to do things that are distasteful to us. Is any right or interest absolute? We limit free speech, prosecuting the person who shouts “Fire!” in a crowded theatre with limited egress. “Rights” must always yield to consequences. Lost lives hurt a lot more than bent ‘principles’. We must also take responsibility not just for the things that we do, but for the things that we could have done but didn’t and consequently failed to prevent. evil or injustice. We can’t just blame the perpetrator; that’s moral indifference.

I am sure Burke will retort that we had no hand in causing the situation and that we have no responsibility for fixing it.

Do we in the rich, first world countries owe any debt to the 13,000 a day dying of starvation in the third world? I can think of a myriad reasons why it is happening ranging from local greed, an indolent poor, falsely delivered aid, to false religion supporting 700 million cows when only 3 million cattle are used for milk or beef. Yet I still give to charity.

So don’t just have a knee-jerk reaction to torture. Think about the issues. Come to a reasoned answer. Call it ‘coercive questioning’ and imagine how you could save a life or the lives of three hundred passengers in a Boeing half way across the Atlantic.

Thursday, November 11, 2010

Latest on health

It is such a long time that I wrote anything here that most of you must have realized that I have been ill. It is only the side effects of the chemotherapy, but this 4th course has been worse than preceding courses. The main problem has been stomach cramps which come along every 5 minutes and last for 10 seconds, and an overwhelming lethargy so that I sleep for long periods of the day. Now that I have stopped the steroids I am not waking up in the middle of the night. I estimate that I am spending about 12-14 hours asleep each day.

I have thought of lots of things to write about including torture, prisons, del 13q, vitamin D and allografts in CLL, then there is the series on Galatians to finish, so watch this space.

Sunday, November 07, 2010

survival curves

Despite having had cancer for more than two years now, I never look at survival curves for my type of cancer. Why not? Because they are not an appropriate tool for telling me how long I am going to live.

They are useful to scientists and doctors in planning treatment and in recognizing what factors influence outcome, but for the individual patient, this means next to nothing. For example, the latest German CLL 8 trial clearly told us that FCR is a better regimen than FC and that if you have the del 11q adverse marker, then adding rituximab puts your prognosis back with main body of patients with CLL. But nothing tells an individual how long he is going to live.

Indeed, quite a lot of patients who received FC lived longer than quite a lot of patients who received FCR. This was obviously true for a number of reasons - e.g. age, stage, other illnesses, FCR toxicity, IgVH status, del 17p - and many of those reasons were quite unknown to doctor or patient.

Median survivals, simply say that at this time point 50% of the cohort were alive and 50% dead. Although randomizing evens out the differences between whole populations in either arm of a trial, it tells us nothing about one individual in a trial. When CLL patients in a trial are followed until everybody is dead - and that will usually take decades of follow-up - there will almost be a few individuals who got the less preferred treatment who form a small tail to the curve; i.e. are long survivors. Who knows, you or I might be one of them.


It was four months since I had seen my 90-year old mother so last Thursday I decided to visit her. I was feeling quite well after a difficult start to the week so I thought that the 150 mile drive was something I could take in my stride. Was I wrong! By the evening I was exhausted and suffering from severe colicky pain which continued into Friday. Friday was when I was due my induction into the exercise program. Because of the Buscopan I had been taking, my resting pulse rate was 100 and after two minutes on the exercise bike it was 135 and I started fainting. Exercise abandoned and the rest of the day asleep and in pain. Friday is also the nadir for my neutrophil counts.

Saturday was chemotherapy day. I had a headache all day and felt unwell, though there was little to put my finger on. Colic was to be expected from the irinotecan and I had two shots of atropine to counter that. My skin was sore and my hair tender to touch, but I could manage a light meal of cottage cheese and thin ham slices. At bedtime I started shivering and snuggled up with a hot water bottle and two paracetamol. At 1 am I awoke with a drenching sweat and had to change my pyjamas. This morning I am much better even though the pump is still pumping 5-FU into my system.

In retrospect, I wonder if I might have had a staph epidermidis line infection which resolved itself as my neutrophils recovered and the fever was brought down by the paracetamol. In any case I have smeared some fucidic acid cream over the Hickman site. Sorry there hasn't been much blogging recently, but you will see why.

Thursday, November 04, 2010

The evisceration of NICE

Polly Toynbee says, "NICE is one of Labour's best inventions". Proof if ever it was needed that NICE has to go. It is is a truth self-evident to all Guardian readers that whatever Polly Toynbee says is automatically antithetical to all right-thinking people. When Polly pontificates we know what side to take.

I don't suppose Polly has ever sat in on a NICE appraisal so as usual she is talking about something of which she has only theoretical knowledge. I have sat in as an expert witness on five occasions. On almost all occasions NICE has got it wrong at first, though sometimes they have managed to correct their view on appeal.

There are several things wrong with the way NICE goes about their work. First: certain members (though not all) of their committees have an extreme prejudice against pharmaceutical companies. They naturally assume that the company is dishonest. I have even seen committee members accuse expert witnesses of being in the pay of Big Pharma and being made to withdraw the assertion under the threat of legal action.

Second: the choice of their own 'expert witnesses' is sometimes bizarre - eschewing people who have researched and written about the problem in favour of local generalists who have no reputation in the field.

Third: their research is done by health economists and 'teenage scribblers' - young graduates who just review the literature without any experience of treating patients or of the great variety of clinical situations that present themselves. These people have no 'feel' for either the disease or its treatment.

Fourth: despite the assertion that 'post-code prescribing' is a great sin, it is actually extremely sensible. For example, there National Guidelines on sickle cell screening for mothers. This is extremely sensible in Camberwell where there is a very high incidence of people of Afro-Caribbean descent, but very stupid in Bournemouth where almost everybody is 'oppressively' white. In Bournemouth, the major health problem is care for the elderly - especially of Alzheimer's disease. The denial of drugs for early cases was much more unfair in Bournemouth than, say, somewhere like Derby, where the geriatricians have so few old people to look after that they look after people in their 50s.

This new government is committed to localism and I thoroughly approve. Having sat through endless reorganisations I am certain the the NHS was best managed in the period prior to 1974 when local authorities could still influence decisions about the provision of services. If you believe in getting the best health service you can in your local area (which is what most people want - they couldn't care a fig for the problems of people in Glasgow who smoke, drink and feast on deep-fried Mars bars - unless they are Glaswegians), then these new moves to disempower NICE can only he welcomed.

Sicker Americans rescued by expensive healthcare

Are Americans healthier than English people? Certainly not, but they do live slightly longer.

This paradoxical situation is described in a new report in the journal Demography and reported in today's Daily Telegraph. People in the US are twice as likely to contract diabetes and a third more likely to develop cancer than those among similar aged people in England.

The study, co-authored by the Institute for Fiscal Studies in London, involved analysing information from two comparable surveys of people aged 50 and over in the United States and England – 20,000 people in the US Health and Retirement Survey and 12,000 people in the English Longitudinal Survey of Ageing.

They found that on average American people aged 55 to 64 were between a third and a half more likely to suffer from one or more of the following chronic diseases: diabetes, high-blood pressure, heart disease, heart attack, stroke, chronic lung diseases and cancer. Diabetes rates were more than twice as high in the United States as in England (12.07 per cent versus 5.88 per cent) and cancer prevalence was more than third as high in the United States (9.57 per cent compared to 5.48 per cent) for people aged 55 to 64. Despite this, both sets of pensioners had a similar life expectancy (82 for men, 85 for women) with Americans actually living on average a few months longer.

It appears that at least in terms of survival at older ages with chronic disease, the medical system in the United States may be better than the system in England. Why is this? it is a case of throwing more money at a problem. Official figures from the OECD show that America spends 16 per cent of its GDP on health care compared with 8.7 per cent in England. As a result, the American system is much more likely to aggressively screen and treat diseases, no matter how much it costs. Americans are much sicker but they make up for it with much more aggressive and expensive health care.

Tuesday, November 02, 2010

Housing benefit

I am not normally a Sun reader, but they seem to have caught out the BBC in an open piece of propaganda based on a lie. Last Thursday the BBC's News at Ten painted a James Van-Cliff as a hard-working individual whose desperate attempt to get back on his feet was being scuppered by an uncaring coalition government. My wife felt quite sympathetic towards him. If they cut housing benefit, young men like that will be living on the street in cardboard boxes.

In fact, it was all a lie. James Lansdale, the BBC Deputy political editor, had contacted a housing charity for a good example of someone who would illustrate a piece he was doing to demonstrate how unpleasant the the government cuts would be. Lansdale was not looking for evidence, just an illustration. He knows the power of anecdotes and he had already made up his mind what the effects of the cuts would be.

James Van-Cliff told the BBC he faced eviction from his council flat and a life on the streets because David Cameron's housing benefit reforms will leave him unable to pay his rent and bills. He told the BBC he "worked his butt off" to get the flat.

It was all untrue. Van-Cliff has now admitted he quit his last job because the £93 weekly pay was not good enough. I agree that £93 a week is not good enough, but even if he were earning no more than the minimum wage, it only amounts to 16 hours work a week - the maximum amount you can do without losing your benefits. So, even when he was working, he was not working all the hours he could. His job was cleaning an office and there are plenty of such jobs in London. My sister-in-law works as a cleaner. But she does three cleaning jobs to ensure that she makes enough to have a family income with my brother of more than the average. Their taxes pay Mr Van-Cliff's benefit payments. They are not best pleased.

He said: "I'm better off on benefits to tell the truth. I'm not going to work on minimum wage for sh*t money. That won't keep me going." The Sun comments "Art school dropout Van-Cliff confessed when The Sun visited him at his £9-a-week flat, where he and jobless girlfriend Charlotte, 18, were idling away the hours by chain-smoking and watching daytime TV."

I can't believe that you can get a flat in London for £9 a week; perhaps it is a misprint for £90? Even that would be cheap, though perhaps a one bed flat in a tower block in Bethnal Green might go for as little as £360 a calender month.

The BBC report claimed the cuts would reduce his benefits by £9 a week - half his food bill - or about a quarter of his cigarette bill. The report failed to reveal Van-Cliff walked out of his job as an office cleaner more than a year ago. He has not had a job since and has worked only four months since leaving school.

He gets a Jobseeker's Allowance of about £51 a week and has applied for £93 a month housing benefit for the flat, which he moved into days before the BBC report.

A BBC spokesman said: ‘We approached a reputable housing association to help us identify someone who might affected by proposed changes to benefit regulations and we interviewed the tenant in good faith. ‘Regardless of his employment status, the individual concerned will be subject to those changes.’ The BBC trying to tough it out.

We are still suffering from a housing bubble. On the back of the miss-selling of subprime mortgages, house prices rose to ridiculous levels. The house that we bought 35 years ago for £26000 was valued at over £600,000. Inflation has eaten away at the value of money over those years, but not by that much. First time buyers were squeezed out of the market and many, apparently rich house-owners took equity out of their property. The wiser among them used the money to put their children in houses, other spent on Chinese consumer goods. Some bought second properties to rent out to those too poor to buy.

This buy-to-let bandwagon was soon giving annual returns of 16% and since mortgage lending rates have fallen to a new low many returns are even higher. Housing prices are beginning to fall,but the banks are not lending and they clearly have some way to go. People are going to have to take a hit over negative equity. At the same time, withdrawal of housing benefit ought to put a brake on rents. Getting the unemployable out of high rent districts will enhance the process. After all, If you won't work, then you might as well not work in Hull or Middlesboro as central London.

A driver for house price inflation has been an increasing population and no new social housing built. In the last year of Gordon Brown, only 16,000 units of social housing was built; back in the 1950s they were building over 300,000. Yet there is plenty of unused property in the UK and at a cost of less than £25000 a unit, most could be turned into affordable homes. Not many would be in central London, though, And if they are not next door to a Fleet Street pub, how would the journalists ever find out about it?