Essays by Malcolm Kendrick, MD
(originally published in RedFlagsDaily)



The Zocor Debacle - I Told You So! But The Great Ship “Cholesterol-Lowering” Has Ripped Its Guts Out On The Harsh Rocks Of Evidence, But Still It Does Not Sink

He Who Pays the Piper Calls The Tune

Thank God He Didn't Die of Heart Disease Doctor

‘Armed and Dangerous’ – Wake up Call

Time For A Conspiracy Theory Or Two. ‘Pharmaceutical Industry Opposition to Reimportation 'Financial Suicide,' Pfizer's Rost Says

Stopping Statins is Bad For Your Health

Gosh, Really, You Don´t Say Are medical journals corrupted?

Statins And Cancer. (Now It Is Getting Silly) 

Horray - Sort Of  Working for drug companies’ – what does that mean? 

A Small Ray of Sunshine About medical societies and ?industry sponsorship

Spotting the Sleigh Of Hand

Statins and Dementia 

Too little, too late Can we believe in medical science?

Temporarily Able Are there any healthy people out there?

What Tangled Webs We Weave. Who to believe in medical science

More Grist To The Grill. About stress and the heart

The Constant Gardener. About drug company morale

ASCOT–BPLA (Another Stupid Commercially Overhyped Trial – Before Prescribing Look Again)

Reflections On Scientific Dogma  Thoughts around the new Nobel Prize winners

Justice Saves Lives  About stress and heart disease


More essays by Malcolm Kendrick

Winter 2005

The Zocor Debacle - I Told You So! But The Great Ship “Cholesterol-Lowering” Has Ripped Its Guts Out On The Harsh Rocks Of Evidence, But Still It Does Not Sink

By Red Flags Columnist, Dr. Malcolm Kendrick

( email - malcolm@llp.org.uk )

Oh, the joy. Just how annoying can I be now? After the PROVE-IT and REVERSE trials comes the A to Z trial, looking at aggressive high-dose Simvastatin treatment vs. low-dose. And I have just been proved right.

‘Munich, Germany - The Z phase of the Aggrastat to Zocor (A to Z) study has shown disappointing results...Treatment with high-dose simvastatin (Zocor®, Merck) failed to show a significant reduction in the primary composite end point of cardiovascular death, MI, readmission for ACS , or stroke. In addition, the high-dose statin regimen was associated with a higher rate of myopathy and rhabdomyolysis.’

I think I made the point some time ago that, if you wanted to prove that the more you lowered cholesterol, the greater the protection against heart disease would be, then a basic requirement would be to use the same drug at different doses - unlike PROVE-IT and REVERSE, which used different drugs at different doses, thus introducing two variables into the equation.

To quote myself from a previous column in Red Flags, ‘ Prove-IT Proved What?’

'I suppose the most basic problem with the (PROVE-IT) study is the old ‘two variables’ conundrum. It is true that those with the greatest LDL lowering were protected against death. However, as you may have noticed, those who were protected not only had a greater degree of LDL lowering, THEY WERE ALSO ON A DIFFERENT DRUG!..... which is rather important, yet seems to have been swept aside on a wave of hype.


In reality, if you really want to prove that the more you lower the LDL level, the greater the protection, then you must use the same drug. This achieves an absolutely critical requirement of any scientific experiment, which is to remove all possible uncontrolled variables.'

Now, the experiment has been done. Someone did use the same drug at different doses, achieving different degrees of cholesterol lowering and, hey presto, no difference in CHD rates. Which proves two things:

Firstly:  The degree of LDL lowering has no impact on CHD

Secondly: Atorvastatin has direct anti-CHD effects that are better than pravastatin

I feel the urge to climb up a local hill nearby with a loudspeaker in hand and bellow to all and sundry, ‘I told you so.’ Unfortunately, the local sheep population is unlikely to be impressed. And I may find myself arrested by the local constabulary.

More frustrating, however, is the fact that this trial will have absolutely, and I mean absolutely, no impact on the prevailing orthodoxy. Already, the powers that be have decreed the following:

‘Despite these surprising findings, experts say these results should not detract from previous studies showing a strong benefit with early and aggressive statin therapy. They continue to recommend early aggressive lipid-lowering therapy to reduce the risk of future cardiovascular events but expressed caution over the 80-mg dose of simvastatin.’

Here was the (close to) perfect study designed to demonstrate that the more you lower cholesterol the more you will protect against CHD. It completely and utterly contradicted the hypothesis. Yet, experts will continue to recommend early aggressive lipid-lowering therapy – based on the hopelessly flawed trials. Ye Gods.

I am overcome by a sense of impotent rage. ‘I told you so,’ has already turned into the bitter ashes of defeat. The great ship, ‘Cholesterol-Lowering,’ has ripped its guts out on the harsh rocks of evidence, but still it does not sink. I am beginning to believe that it is unsinkable.



January 16, 2005


(French Proverb)

By Red Flags Columnist, Dr. Malcolm Kendrick
( email - malcolm@llp.org.uk )

And what song do we expect the pharmaceutical company wishes to hear sung by international medical opinion leaders? In general it goes like this ‘Use more of the new expensive drugs. For they will make you well.’ To the tune of Amazing Grace.

How much money does it take to get an international opinion leader to sing for their supper? That depends. In the case of Dr Bryan Brewer, a leader at the National Institutes of Health, it took $57,000/year.

Brewer, as a leader at the NIH was part of a team that gave the nation new cholesterol guidelines that were expected to prompt millions more people to take the daily pill. He also has written favourably of a specific brand of cholesterol medication, Crestor, which recently proved controversial.

What doctors were not told for years is this. While making recommendations in the name of the NIH, Brewer was working for the companies that sell the drugs. Government and company records show that from 2001 to 2003, he accepted about $114,000 in consulting fees from four companies making or developing cholesterol medications, including $31,000 from the maker of Crestor (AstraZeneca)LA Times Jan 11, 2005

However, this is relative peanuts compared to Dr P.Trey Sunderland III, a senior psychiatric researcher at the NIH. He took $508,500 in fees from Pfizer Inc. whilst collaborating with them, and endorsing their drug.

But these two are not, in any way, unique. Medical opinion leaders, those who put their names to the research and claim to write the clinical papers (you don’t believe they actually write clinical papers do you? – how touchingly naive) are all paid very large sums of money by the pharmaceutical industry.

Quite how much they get paid is somewhat difficult to ascertain. The exact amounts will remain a well-guarded secret between the opinion leader and their accountant. But I have been involved in doling out such payments, and the amounts soon add-up.

One of the best scams is that an opinion leader will be invited to talk, or present, at a major medical meeting. There are certain individuals who travel and talk all over the world. They will then be invited by another company to talk at the same meeting. Then another company, then another. A conversation ensues which goes something like this:

Opinion leader (having already had five other invitations): ‘I like to book my own travel, so just send me the money for an air-fare, first class, eight thousand dollars. Thank you.’ (The ‘Thank you’ is optional, and rarely used).

Do the maths. If one company is already flying an opinion leader to a meeting, and he Hoovers up five sets of air-fares from other companies, he – for it is almost always a he - can make forty thousand dollars in air-fares before the meeting even starts.

To be fair to the pharmaceutical companies, they can, and do, become somewhat enraged by such behaviour. But they are usually so terrified of upsetting a big cheese, who may then walk over to another company, that they just pay up anyway.

What really makes pharmaceutical companies mad is when an opinion leader agrees to chair two meetings – at the same time. I have been to a meeting when the chairman walked out, went across the corridor, and introduced a meeting – for another company – before returning. Then spent three hours dotting between the two meetings. An impressive display of juggling no doubt, but I don’t think the companies involved were terribly impressed.

What’s the going rate for such activities? The figures vary. Cardiology seems to be the biggest payer, and the highest fee I have heard of was $20,000 to chair a two hour meeting. You must remember that this is $20,000 plus air fares, accommodation, drinks, meals, entertainment etc. and this individual would also have been taking part in advisory boards, presenting at other symposia etc. It is not impossible for a top level opinion leader to make $100,000 during a five day meeting.

Fair enough, these are hugely hard working, highly intelligent individuals at the top of their profession. What they are paid is peanuts relative to a CEO of a major company. Why shouldn’t they demand, and get, huge fees?

No reason, except that these are the people who advise the NIH and the FDA. They also write the guidelines which set the standards for more humble doctors to follow. They, basically, decide which drugs are good and bad, and what treatment should be followed. In the end, what they say flows down and defines the drugs that your doctor will prescribe to you. We hope, and expect, that such advice will be untainted by commercial considerations. Some hope.

When the latest National Cholesterol Education Panel (NCEP) guidelines were unveiled, none of the panel members disclosed any affiliation to the pharmaceutical industry. I was part of a group (the centre for science in the public interest CSPI) who wrote to the National Heart Lung and Blood Institute (NHLBI) – the group under which the NCEP operates. (NHLBI is part of the National Institutes for Health). We had a number of objections, but number one was that no financial disclosures had been made.

Surprise, surprise, it turned out that every single member of the NCEP panel had close association with statin manufacturers, and had been paid varying – huge – sums of money by them. We thought you knew, bleated Dr Barbara Alving for the NHLBI.

In addition, as Dr Alving wrote in response. ‘Individuals who are most expert in a subject area are the ones most suitable to serve on a guideline panel for assessing the science and developing clinical recommendations. They are also often the very people whose advice is sought by industry.’

True, Dr Alving, but there are people out there - for e.g. Uffe Ravnskov – to pluck a name from the air - who has written a book, and hundreds of articles, critical of the idea that lowering cholesterol with statins is a good thing. He is an expert in this area – even if his views make him somewhat of a scientific pariah. Was he asked to take part in the creation of guidelines to bring some much needed balance to the discussions?

No, the only people chosen were the people who were absolutely and completely in favour of prescribing statins, and who were all being paid vast sums of money by statin manufacturers. The reality is that anyone who dares to criticise the established dogma will never be invited, never, ever. There are no critical voices, no discussion of the central issues. In this way dissent is, effectively crushed. And this is true of all therapy areas.

Currently the situation is thus:

It is almost impossible to become an ‘opinion leader’ unless you do the clinical trials paid for by the pharmaceutical industry. These are the biggest, highest profile studies, and the results are presented at major medical meetings, and published in the high profile medical journals.

Ergo, opinion leaders are almost all supported and promoted by the industry. From the very start, they are a self-selected group. Pro-industry, pro-drug use. Usually, pro-specific drug.

These people write the editorials and speak to the press and take part in discussion and symposia and presentations. They are then invited onto prestigious committees that decide on the medical treatment for all of us.

I am sure that they don’t think they are biased at all. But they come with built-in bias. In my opinion, they should be kept a million miles away from any decisions on guidelines, but because there are no other ‘experts’ out there, they are always and inevitably chosen - ‘Who else is there?’ And because of this we end up with madness. I shall leave you with an example of such madness.

A group of doctors in Norway decided to review the 2003 European guidelines on blood pressure and cholesterol lowering. Norway, as you may or may not know, is one of the healthiest countries in the World, with one of the longest life expectancies. It was also rated as having the highest quality of life in the World. People in Norway are extremely healthy and pretty wealthy. The rate of death from heart disease has also fallen dramatically over the last thirty years or so.

Here is a country, surely, that should be reasonably content with their overall health.

Not so, not so at all. According to the guidelines, by the age of twenty-four, 50% of Norwegian men had a blood pressure, or cholesterol level requiring drug treatment. By the age of forty nine, this had risen to 90%. Getz L et al. Scand J Prim Care 2004.

Ninety per cent of Norwegian men aged forty nine need to take drugs for the rest of their lives! If this isn’t medical madness, then I cannot imagine what is. And it is a guideline based madness that can be directly traced back to a group of ‘highly objective’ experts who have all been paid extremely large sums of money by pharmaceutical companies who make blood pressure and cholesterol lowering drugs.

I cannot for the life of me think of any other area of human enterprise whereby someone who is paid enormous sums of money by a commercial organisation would be allowed to set the standards in which those commercial organisations operate. Let alone an area of such importance. The closest analogy I can think of would be a judge, who had been paid a million dollars by Microsoft, being asked to sit to preside over an anti-trust suit against Microsoft. (I thought of writing Mafia instead of Microsoft, but lost the nerve).

No judge would ever be allowed to pass judgement over an organisation that had just paid him several hundred thousand dollars, with more to come – assuming the ‘correct’ verdict was reached. It would never, ever, be allowed. (Yes I know it probably happens, but you are supposed to try and keep quiet about it, otherwise you end up in jail).

Yet in medicine this happens all day, every day. It’s utterly flagrant, and no-one even bothers to try and hide it. In my opinion, it is a complete and total and absolute scandal. It is corrupt, and it should be illegal.…. I am not holding my breath for any action any time soon.



March 24, 2005


By Red Flags Columnist, Dr. Malcolm Kendrick
( email - malcolm@llp.org.uk )

There are those of us, poor misguided fools, who believe that the main point of taking drugs is to prevent an early death. We are clearly wrong. The important thing is that you must not die of heart disease. For dying of heart disease is clearly much worse than dying of something else.

I don’t know, for myself, I think a major unexpected heart attack is not a bad way to go. A sudden sharp crushing pain, then it all goes dark, then – well who knows actually. Not that pleasant, but this is a better way to go, surely, than a slow agonising death from cancer. Or maybe not, maybe we should all have a chance to prepare for death, get used to the idea….. discuss.

These idle thoughts were prompted by (Yet Another Damned study YADs) demonstrating that if you give a very high dose of statins, you can reduce the chance of dying of CHD – a bit – compared to a standard dose of statins. However, the overall mortality rate is unchanged.

My first response to this study, the TNT trial, was “quelle surprise!” My second response was “I bet this results in yet more demands for ever greater cholesterol lowering.” I was not to be disappointed.

"In summary, our findings demonstrate that the use of an 80-mg dose of atorvastatin to reduce LDL cholesterol levels to 77 mg/dL provides additional clinical benefit in patients with stable CHD…. write Dr John C LaRosa (State University of New York Health Science Center, Brooklyn) and colleagues. "These data confirm and extend the growing body of evidence indicating that lowering LDL cholesterol levels well below currently recommended levels can have clinical benefit."

A stance fully supported by Eric (rent a quote) Topol.  "There isn't any question left at this point that we should be more aggressive," The Washington Post reports.

Oh Eric, Eric, Eric. You are just so predictable. Still, I suppose that you own, and run, a major cardiology website http://www.theheart.org which is almost completely supported by ‘unrestricted educational grants’ from AstraZeneca. AstraZeneca makes Crestor, and their marketing strategy is to push for greater and greater cholesterol/LDL lowering. So it would be a bit much to expect Eric to err on the side of caution. ‘Statinate and be damned’ would be his family motto. That mad tilter at the windmills of conventional thought.

And why does Eric, sorry AstraZeneca, promote aggressive LDL lowering? Because Crestor is the most potent statin of all. How do we know this? Because AstraZeneca keeps having to send out warnings to doctors about toxic side-effects. Good old Crestor, or as I call it, ‘Drug on the Green Mile.’ Anyway, I think we should all just take the things that Eric Topol says with a little pinch of salt – just to keep the blood pressure up.

But still, to return to the main point. Does the TNT trial (Treating to New Targets), really support the use of high dose statins? Well, if you want to create liver problems and reduce the chances of dying of heart disease – yes.

If you want to prevent death…. Not really. And don’t just take my word for it.

In an editorial accompanying the TFT study in the NEJM Dr Bertram Pitt (University of Michigan School of Medicine, Ann Arbor) thought that clinicians will need to look critically at the TNT data to determine whether the results are sufficient to alter clinical practice.

Pitt managed to spot that there were no differences in overall mortality between the two therapies and even an increase (my italics) in the number of deaths from noncardiovascular causes in those treated with atorvastatin 80.

Well, Bertram, if there were fewer deaths from cardiovascular disease, and no differences in overall mortality, it doesn’t take Albert Einstein to work out that there may have been an increase in deaths from other causes. No need to fire up the super-computer to figure that sum.

He notes (the clever chap that he is) that while the number of deaths from CHD was reduced by 26 among patients assigned to high-dose atorvastatin, the number of deaths from noncardiovascular causes increased by 31. ‘While this increase in noncardiovascular events may be due to chance, it is still a matter of concern.’ he noted (wisely).

But the best bit is yet to come. This next commentary is quoted directly from theheart.org

Specifically, Pitt takes issue with the lack of observed differences in overall mortality, although he concedes that the study was not adequately powered to observe differences in this end point. For differences in mortality to be observed, investigators would have needed to enrol approximately 34 000 patients, something TNT investigators say would have been very difficult.

"We need to make the assumption that mortality has been proven, that LDL lowering does in fact lower total mortality rates," said LaRosa.

We need to make the assumption that mortality has been proven…….. Why, exactly, do we need to make this assumption? No study, ever, on primary prevention of heart disease with statins has ever shown a reduction in overall mortality. None, ever. And there have been many. And assuming something so absolutely vital, based on a huge amount of contradictory evidence seems just a tad premature.

I think I shall make an observation, rather than an assumption. As no clinical trial on cholesterol lowering in primary prevention of heart disease using statins (or any other drug actually) has ever demonstrated a reduction in overall mortality, it can be stated categorically that statins have no effect on overall mortality.

But now to talk statistics……run for cover, save the children.

Pitt concedes that the study was not adequately powered to observe differences in this end point (overall mortality).’

Now I am not a statistician – my brain fuses when confronted with mathematical formulae. But I do clearly understand the overall concepts. And I shall try to explain why the comment that the study was ‘not adequately powered to observe differences in this end-point,’ is bonkers. And can only be accepted if you are the sort of person who thinks that the Bill Clinton defence ‘But what is, is?’ sounds reasonable.

Almost all clinical trials need to enrol a sufficient number of people, over a sufficient time period, to show a significant difference between the ‘intervention’ group, and the ‘standard’ group. The greater the difference you expect to see, the less people you need to enrol. For example, if you expect that everyone who takes the drug will live, and everyone who doesn’t, will die, then it doesn’t take that many people to demonstrate a significant difference.

In my own mind I liken this to throwing a die to find out if it is ‘weighted’ or not. If the die is heavily weighted it will come up with a six almost every time, and it doesn’t take long to work out that you have a biased die on your hands. However, if the die is only very slightly weighted, it may take hundreds of throws before you can be sure that it is coming up six more times than is possible by chance.

Statisticians basically try to work out – before the trial starts – how many people you need to treat, for how long, to see if the die is weighted. Or if it is not. Or by how much the die is weighted. So you need to estimate, before the trial starts, what difference you think you are likely to find, then you can work backwards from this to establish how many patients you need for the trial to be properly ‘powered’ (with a bit of a buffer built in).

If the trial is insufficiently ‘powered’ i.e. doesn’t have enough people in it, you may see a difference, but it will not be statistically significant i.e. the difference could have been a ‘chance’ finding.

Still awake? Good.

Here is where we hit the ultimate Catch 22. The almost perfectly bonkers loop of self-referential logic in the TNT trial.

Step One – of mad logic:

Statins have been shown to reduce cardiovascular mortality in primary prevention studies (that is, in people who have not already got established heart disease). So a statistician, knowing this can say we need to look at (in the case of the TNT study) ten thousand people, with five thousand in one ‘arm’ of the study and five thousand in the other ‘arm’ over about five years or so. That is, if we expect to see around a 20% relative reduction in deaths from cardiovascular disease.

Step Two – of mad logic:

Because statins have not been shown to reduce overall morality by much, if at all, we need a far greater number of patients in the trial to ‘power’ it, in order to see a significant reduction in overall mortality. In the case of TNT, at least 34,000 patients - apparently.

Step three – of mad logic:

When the study shows a reduction in cardiovascular mortality this is claimed to be statistically significant.

Step four – of mad logic:

When the study shows no difference in overall mortality, it can be confidently stated (without being struck down by a bolt of lightening from above) that the study was not powered to look at overall mortality, and therefore the finding could have been ‘chance’ and is not significant.

This is despite the fact that, in the TNT study, more people died of non-cardiovascular disease than cardiovascular disease, and that more people, total, died in the statin ‘treatment’ arm. This, we are told, is chance. Whereas the much smaller overall reduction in cardiovascular mortality is statistically significant.

And lo, the greater number of deaths is insignificant. Whilst the lesser number of deaths is significant. And the statistician looked upon his work and he was pleased. And because no one understands statistics, and they are terrified of making a statement that may make them seem foolish, we accept this complete rubbish without question.

Of course, accepting this rubbish does allow various doctors to make statements such as the ones that follow:

This study provides direct evidence of benefit of intensive treatment in stable coronary heart disease patients, a population that numbers about 30 million in the US. That's huge.’ Dr Christopher Cannon (Brigham and Women's Hospital, Boston, MA)

He went on to add: ‘To be able to prevent major cardiovascular events on this scale will have a huge public-health implication.’

Or how about a little more from John La Rosa  (State University of New York Health Science Center, Brooklyn).

The results of the TNT study indicate that the linear relationship between reduced LDL and reduced CHD risk demonstrated in prior secondary-prevention trials holds true even at very low LDL cholesterol levels. These data extend the growing body of evidence that lower LDL cholesterol levels well below the currently recommended targets can further reduce the healthcare burden associated with cardiovascular and cerebrovascular disability.’

And they can still sleep in their beds at night. Cor blimey – as we say in the UK.



April 19, 2005

‘Armed and Dangerous’ – Wake up Call

Many a man stumbles across the truth, then picks himself up and hurries on as though nothing had happened.” Winston Churchill

By Red Flags Columnist, Dr. Malcolm Kendrick
( email - malcolm@llp.org.uk )

For some time now, I have been following the work of a UK parliamentary committee which has been looking into the activities of the pharmaceutical companies, and their influence over the healthcare system. Whilst this committee was sitting you could even watch the proceedings on television, although I wouldn’t recommend it - other than as a cure for insomnia.

Despite the superficial slowness and dryness, the conclusions were, in fact, rather dramatic. And last week, the British Medical Journal (BMJ) woke up and took notice, and wrote a series of articles based on the committee’s findings. You can see the resultant editorial ‘Say no to the free lunch,’ here.

The BMJ didn’t’ pull any punches.

The power of drug companies to buy influence over every key group in health care—doctors, charities, patient groups, journalists, politicians—has clearly shocked a UK parliamentary committee. It should shock us all. Can we console ourselves that companies' lavish spending on research and marketing, which far outstrips spending on independent research and drug information, leads to truly innovative treatments? No, says the committee's report. Can we rely on regulatory bodies to keep the industry in check? No, again.

What we can rely on, says Slattery-Moschkau, a former drug rep and creator of a hard hitting new film on the industry, is that drug reps are "armed and dangerous," selected for their ability to seduce and persuade rather than their scientific skills, and armed with, among other things, details of your prescribing behaviour.’

I don’t suppose any of this comes as a great surprise to readers of Redflags. Or, frankly, to anyone with the remotest interest in this area. As we all know, for years the industry has been infiltrating and influencing every nook and cranny of the healthcare system, from medical societies, to regulatory bodies, even ownership of accredited medical education providers.

Various ‘troublemakers’, like Nick Regush had been warning us all about this for many years; and for many years their warnings have been smoothly brushed aside by the medical ‘establishment’, only too eager to see the lucrative status quo maintained. Opinion leaders, for example, have constantly reassured us of their complete scientific objectivity, maintained at huge personal cost in the face of merciless bombardment by extremely large sums of money. A mental state, incidentally, that the BMJ characterises as ‘professional self-delusion.’

Of course, one UK parliamentary committee report, even with the support of the BMJ, will not change the world. But this is far from the first attack. In the USA, the FDA and the NIH have been reeling under some pretty heavy artillery fire as the close connections between these regulatory bodies and industry have been exposed.

So, are we now at the high water mark? Have we reached that moment when everyone finally wakes up, looks around and thinks, ‘my God, this has gone too far?’ Or is this just another spasm of self-righteousness that will pass. A case of the establishment suddenly ‘stumbling across the truth, only to pick itself up and hurry along as though nothing had happened?’

Watch this space for further developments.


May 8 2005


‘Pharmaceutical Industry Opposition to Reimportation 'Financial Suicide,' Pfizer's Rost Says

‘Pharmaceutical companies are being led by "dinosaurs who are committing financial suicide" by opposing US residents' reimportation of lower-cost drugs from abroad, Peter Rost, a vice president of marketing at... Pfizer, said in a speech at the Minnesota Senior Federation Monday, the Minneapolis Star Tribune reports.

Rost is an advocate of reimportation who has testified before Congress twice in recent months in favor of legalizing the practice. In his speech, Rost said, "Getting drugs to people who need them is about right and wrong. When millions of uninsured older or poor Americans get sick because they can't afford their medications, that is morally wrong." He noted that most U.S. residents pay prices for medications similar to prices paid in Europe because U.S. insurers negotiate bulk discounts, but uninsured people in the United States "pay the full price -- twice what you'd pay in Europe." Rost added, "Everybody negotiates bulk prices for bulk deliveries, everybody but the United States." He also said that pharmaceutical companies could increase profits by lowering prices and boosting sales to low-income U.S. residents. Rost said he once doubled sales in Nordic countries for a pharmaceutical company he previously worked for after he lowered prescription drug prices. The Star Tribune notes that Pfizer officials say the company "disagrees strongly with Rost's views" (Wolfe, Minneapolis Star Tribune, 5/3).

I picked up this story this morning and blinked twice. I thought it was worth re-printing in full, so that you could run it around the glass a few times and inhale the heady fumes.

A man who works for Pfizer making a speech about pharmaceutical company issues that Pfizer strongly disagrees with! Call me an old sentimentalist if you like, but in my day if you made public statements that your company strongly disagreed with, your employment future could me measured in nanoseconds. Actually a nanosecond would be a bit long, but I can’t remember what is shorter than a nanosecond. A picosecond, a femtosecond?

Either Peter Rost is very near retirement, or he already has another job lined up, or has gone bonkers…. But he has testified before Congress twice in recent months…. And Pfizer still haven’t booted him out. Does he have the negatives of Pfizer’s CEO in compromising positions?

Or do my antennae twitch to the faint signal of ‘evil pharma conspiracy?’ (No offence to the pharma industry obviously).

I suggest the following conspiracy theory. It goes as follows…

Reimportation cannot be stopped, and trying to stop it is ripping apart any final shreds of goodwill felt towards the pharmaceutical industry. Thus, Pfizer are repositioning themselves for the inevitable. So they are allowing one of their own to slam the industry position on reimportation, who will then be in a good position to act on behalf of Pfizer in any coming discussions. He will be seen as a ‘good guy,’ on the side of the patients, and will be able to get away with twisting the new situation (whatever that may be) in favour of Pfizer.

You think that I have become too paranoid? Seeing conspiracy where there is none?

What is the alternative? That Pfizer have become such a benevolent organisation that they are quite content for one of their employees to act, and speak, against their best interests, potentially helping to ensure that Pfizer lose billions of dollars through re-importation?

Now that truly would be incredible.

So, what’s the choice? Pfizer don’t care about public statements made by their employees that may cause them serious financial damage? Or, Peter Rost is acting with the full support of Pfizer, and his statements are part of company strategy? Frankly, it’s a no brainer.

‘Oh, what tangled webs we weave, when we practice to deceive.’



  May 17, 2005 


A kind reader just sent me a link to an article in Geriatrics

It was entitled, ‘stopping statins is bad for your health.’ I’m afraid to say that it isn’t new news, as it came out in October last year, but it is news to me. And it is such a mind-bogglingly stupid article that it demands some comment.

It was written by one Frederick T. Sherman, who has no financial connections with the pharmaceutical industry to disclose. So here is a little challenge to readers of Red Flags. Find the financial connection between Frederick T. Sherman and a statin manufacturer and win a prize. (The prize being a sense of smug moral satisfaction – do you think I am made of money?)

By the way, the fact that there is a great big banner ad for Lipitor at the top of the web page, and a socking great ad for Caduet running down the side, doesn’t count. Just because Pfizer provides advertising revenue to a journal that Frederick T. Sherman gets paid to write for is far too easy.

Moving on. The main theme of this article is Bill Clinton, and his heart attack, and quadruple bypass. Apparently, in 1992 he had been found to have an LDL level of 177 – oh, my God. Luckily, his eagle eyed doctor had started him on Simvastatin … in 2001. Glad to see the medical profession leaping into immediate action.

But naughty, naughty Bill stopped taking his statin, and had a heart attack in 2004. Or maybe he didn’t have a heart attack, but just had blocked up arteries – this bit isn’t too clear. Why did Bill stop taking his statin? Because he felt he was taking exercise and losing weight, and didn’t need to take a statin any more.

Now, I’m not one to judge – as my mother-in-law is wont to say, before doling out a metaphysical death sentence – but Bill really ought to know better. I know that diet and exercise are supposed to be the first actions taken for those with high LDL levels, before taking drugs. But once you’re on drugs, you really ought to take them forever, and ever, and ever.

As William T. Sherman would say:

‘Clearly, long-term compliance with medications, specifically statins, is more important than diet and exercise alone. Drug therapy, rather than lifestyle modification, must become the mainstay of therapy for the primary and secondary prevention of CAD. The future coronary health of the American public depends upon Baby Boomers and subsequent generations taking all of their cardioprotective medications for life.’

Read that paragraph you naughty people you. Exercise all you like, lose all the weight you can, but it will make no difference. YOU MUST TAKE YOUR STATINS. Now, go to bed and no pudding for you.

A small issue William T. Sherman noted is that, in 1992, Bill Clinton had an LDL level of 177. In 2004, it was 114. Excuse me, William T. Sherman, but does it not seem odd to you that Bill Clinton had achieved an LDL reduction of 35%, having stopped his statin. A 35% reduction in LDL would be considered a therapeutic ‘success,’ for the statinators amongst us.

So, without a statin Bill Clinton’s LDL fell by 35%, then he had a heart attack. Forgive me for saying this William T. Sherman, but to my mind this would appear to suggest that a falling LDL level is a risk factor for CHD – as clearly demonstrated in the Framingham study, amongst others.

In the unforgiving logical prison that I inhabit, the parable of Bill Clinton would not seem to be a warning against stopping statins. It seems more likely to be a warning that when your LDL level falls, you are in serious danger of suffering a heart attack. However, I tend to find that one’s interpretation of events can be clouded by external funding issues.

Anyway, thank you to William T. Sherman for reminding us that ‘The future coronary health of the American public depends upon Baby Boomers and subsequent generations taking all of their cardioprotective medications for life.’

There is just no answer to that – at least not before the children have safely gone to bed.



   May 22, 2005 


Sometimes you read something of such blinding obviousness (if that is actually a word), that you wonder why anyone even bothered writing it at all. You know the sort of thing  - ‘constant criticism of children does not lead to a sense of self-worth.’ ‘A centralized command economy does not create wealth for citizens.’

But the blindingly obvious can be critically important depending on who says it. I can bang on and on about the fact that medical journals have basically turned themselves into advertorials for the pharmaceutical industry, and be readily dismissed as a fringe lunatic.

However when Richard Smith, editor of the BMJ for many years who resigned last year, says it, then it would seem that even the cosy ‘establishment’ may be starting to feel the first cold fingers of doubt creeping in. Perhaps things really have started to go too far. So read and enjoy an article from the BMJ 21st May 2005.

‘Medical journals are no more than “an extension of the marketing arm of pharmaceutical companies” because a large proportion of their revenue comes from drug advertisements and reprints of company funded trials, claims former BMJ editor, Richard Smith.

Dr. Smith argues that although medical journals make a sizeable income from drug advertisements this is the least of their “corrupting form of dependence” on the industry, since the advertisements are “there for all to see and criticize”

Dr Smith’s strongest criticism is levelled at the fact that journals publish clinical trials that are funded by the industry. Unlike advertisements, trials are seen by readers as the highest form of evidence, he says. Trials funded by drug companies rarely produce unfavourable results and make up between two thirds and three quarters of the trials published in key journals.’

Will this change anything?….. You have GOT to be joking.



May 24, 2005


By Red Flags Columnist, Dr. Malcolm Kendrick

I was not sure whether to even bother responding to the latest news that statins prevent breast cancer. But I think I must, as I believe we are now entering very dangerous ground with statins. We are moving beyond accentuating the positive towards a total distortion of the facts. Over the last year or so, I have seen articles stating that statins prevent Alzheimer’s, prostate cancer, heart failure and now breast cancer. I have seen, and groaned.

"When we looked at statin use prior to breast cancer, what we found was that users of statins were 51 per cent less likely to develop breast cancer as opposed to those who were not using a statin," Dr Khurana said.

How, you may ask, can this be true when the latest TNT study, CARE, J-LIT, ASCOT-LLA and other too numerous to mention seemed to show a significant trend towards increased cancer in those taking statins.

The answer is that these studies are not mutually contradictory – just the way they are interpreted. Dr Khurana’s study was not a placebo controlled clinical trial. He, and his team, merely looked at forty thousand women, and found that those given statins were less likely to have breast cancer.

He decided to interpret this as possible proof that statins protect against cancer. But there are three possible explanations for this finding:

·    Chance

·    Statins protect against breast cancer

·    Women given statins were less likely to get breast cancer in the first place

Explanation one is possible, but uninteresting. Explanation two would contradict many of the statin trails, where rates of cancer were higher in those taking statins. Ergo, it seems unlikely to be correct.

Explanation three, however, fits what is already known about cholesterol levels, statins and cancer risk. Firstly, we know that those given statins will have higher cholesterol levels than those not given statins. Secondly, study after study has shown that people with high cholesterol levels are at a greatly reduced risk of cancer.

You may have seen the study in Geriatrics earlier this year demonstrating that, in the elderly, a low cholesterol level was associated with a doubled risk of death – from all causes - especially cancer. A much, much bigger study was done in Austria, looking at cholesterol levels vs. risk of death. One hundred and fifty thousand people were studied over fifteen years.

‘In men, across the entire age range, although of borderline significance under the age of 50, and in women from the age of 50 onward only, low cholesterol was significantly associated with all-cause mortality, showing significant associations with death through cancer, liver diseases, and mental diseases.’

So, we give statins to a group of women who – because they have high cholesterol levels – are at a significantly reduced risk of cancer. When they are found to have a lower risk of cancer on statins, we claim that statins reduce the risk of cancer.

We then receive large sums of money from statin manufacturing company X. We then become a respected international opinion leader. We are then asked to sit on committees making up guidelines on the prevention of heart disease. We then act as peer-reviewers for journals so that when someone writes a letter such as the one below, written to the NEJM – we can reject it.

TO THE EDITOR: La Rosa et al.(1) claim to have shown significant clinical benefit from 80mg of atorvastatin per day compared with 10mg per day. The clinical benefits claimed were solely in selected cardiovascular end points. There was no increase in overall survival since there were more deaths from malignancies and other fatal conditions. For every malignancy that was fatal, or other condition that proved fatal, many more malignancies or other potentially fatal conditions must have been diagnosed. The morbidity from serious non-cardiac conditions is never considered in studies of statins where there is no increase in survival with treatment.

Exchanging a cardiac death for the prolonged misery of death from a malignancy or from another fatal condition can hardly be claimed to be a clinical benefit. The purveyors of the statins need to look with more objectivity at the overall effects of those agents. Even when there is an apparently impressive increase in overall survival, the real gains are negligible (2).

Louis H. Krut, MB.ChB., M.D.

1. La Rosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;323:1425-35.
2. Krut LH. On the statins, correcting plasma lipid levels, and preventing the clinical sequelae of atherosclerotic coronary heart disease. Amer J Cardiol 1998;81:1045-6.


June 16, 2005


By Red Flags Columnist, Dr. Malcolm Kendrick
( email - malcolm@llp.org.uk )

The House of Representatives voted this afternoon to prohibit outside doctors and scientists who work for drug companies from sitting on Food and Drug Administration panels that pass judgment on those same companies' products.

Don’t get me wrong. This is good news……But….but... At present Saddam Hussein sits in a prison cell, awaiting his trial for crimes against humanity. The trial of Slobodan Milosevic (remember him, Kosovo, murder of thousand of Albanians – ring any bells?) has been going on forever, and will go on forever, until Slobodan has to be brought into court preserved in formaldehyde, having died eight hundred years previously. Even then his defence lawyer will still be bleating for more evidence to be heard.

Scientists who work for drug companies….’ Boy, Bill Clinton could argue about the meaning of that phrase for at least as long as it will take for the sun to contract, blow up, shrink back into a red dwarf, before finally become sucked into the centre of the Universe as all the Galaxies contract down to nothingness.

The fact is that corruption is rarely clear-cut. Who gave that order? Was it actually Saddam, did he know anything about it, or was he just practising his sinister smile in the mirror. When he said ‘Exterminate all of them.’ Which them was he referring to?  Was it those them that died, or another them? ‘I put it to the court that them them could not have been those them that died, but were another them entirely.’

And when it comes to ‘working for drug companies’ – what does that mean? Or, what does that mean exactly and precisely? I have worked with ‘International Opinion Leaders’ on many occasions. You would have to be a combination of Sherlock Holmes, Hercule Poirot and Miss Marple to work out the convoluted pathways by which money happens to find its way from the deep coffers of a pharmaceutical company into the construction of a new swimming pool for said opinion leader. But happen it does.

Nothing is written down, nothing that could link Opinion Leader X to Pharmaceutical company Y. There is usually an intermediary involved – a PR company, or medical education company. The company is paid a global sum by the pharmaceutical company, and, in turn, will then pay the opinion leader. ‘I have never been paid by a pharmaceutical company for working on product X.’ Claims opinion leader Z in an indignant huff. Literally true, but at the same time, a blatant lie. If you want the true truth, you must work out what question to ask – very carefully.

Or, in the case of Eric Topol, to name a name. He set up, and owns – via an intermediary company – a website called Theheart.org. This is a well known cardiology site, and has thousands of registered users – almost all of them doctors/cardiologists. It is paid for, entirely, by the pharmaceutical industry.

Does Eric Topol work for the pharmaceutical industry? No he does not. Does he, through his company ownership of Theheart.org, earn hundreds of thousands of sponsorship dollars from the industry - yes. Does he write editorials for the NEJM etc. on the use of various drugs produced by the companies that support his website, without stating his financial links to the Industry - yes?

Would he fulfil the new criteria for sitting on an FDA panel – yes? After all, he doesn’t work for a pharmaceutical company. Should he sit on an FDA panel…..well, gentle reader, I will leave that entirely up to you to decide. But I know what I think.

I know that whoever proposed this bill (Rep. Maurice Hinchey) means to restrict the influence of pharmaceutical companies within the FDA. A wholly laudable aim. But opinion leaders and the industry are so deeply entwined, with so many different and difficult-to-establish links – overt, covert, explicit, implicit, filtered though intermediaries – that working out who is ‘clean’ is extraordinarily difficult.

The industry will easily run rings round a piece of legislation like this. All it may achieve is to drive the relationships between the industry and powerful doctors further from prying eyes.


 June 21, 2005


By Red Flags Columnist, Dr. Malcolm Kendrick
( email - malcolm@llp.org.uk )

Finally, a sign that some ‘Opinion leaders’ may be finding themselves a trifle uncomfortable with the stench of corruption. Nose plugs only work for so long. Here is a clip from an article found in a newsletter sent out to pharmaceutical executives.

Doctors Fight Over Drug Firm Influence

A fierce, behind-the-scenes battle over how much influence drug companies exert on doctors is the raising blood pressure at the American Society of Hypertension.

The society's cofounder and longtime editor of the prestigious American Journal of Hypertension, Dr. John H. Laragh, has accused "academic physician/businessmen" who accept industry speaking and consulting fees of improperly coloring the group's activities.

"The lines separating marketing from education have been fractured," Laragh wrote in an e-mail message to physicians in the 3,000-member society.

The episode is a stark example of a broader debate taking place within the nation's medical societies, which represent physicians in virtually every medical specialty. Recently, many of the groups have become more sensitive to the potential for conflicts of interest relating to pharmaceutical industry grants.

Disagreements have flared over industry money used to support the hypertension society's educational programs, as well as the propriety of direct industry payments to physicians who serve as lecturers and consultants. The hypertension organization requires doctors participating in speaking programs to reveal the payments, but does not require them to disclose amounts.

Critics say the payments help companies put a patina of scientific and medical legitimacy on what is otherwise an attempt to increase market share.

"The society is seen as sort of a marketing tool by industry. There is a lot of money to go around," said Dr. Curt D. Furberg, a former member of its executive council and a professor of public health sciences at Wake Forest University in North Carolina.

Good on you Dr Furberg. You may not know who he is, but he has been making waves for years about the potential for calcium channel blockers (antihypertensives), to increase the overall mortality rate. This has made him particularly unpopular with those companies who make various calcium channel blockers. The word Pfizer springs to mind, for some reason.

It comes as no real surprise to see the academic world of hypertension research hitting the barriers first. Drugs to lower blood pressure were amongst the first to be subjected to massive marketing hype, and ‘opinion leaders’ in this area have had their snouts in the trough for longer than anyone else. Societies, such as the American Society of Hypertension are, basically, pharmaceutical company constructs.

To quote Dr Michael A. Weber (singled out for particular criticism by Dr Laragh).

All medical societies rely heavily on industry sponsorship, Weber said. "Otherwise we wouldn't exist,"

If the American Society of Hypertension wouldn’t exist without industry sponsorship, then maybe it shouldn’t exist at all.

Anyway, I take this article as a small ray of sunshine – a small harbinger of spring in the midst of a bleak winter. Time, I hope, that the pendulum starts to swing back towards humanity and away from pure profit.


June 28, 2005


By Red Flags Columnist, Dr. Malcolm Kendrick
( email - malcolm@llp.org.uk )

A redflags reader wrote me a quick e-mail, with a plea ‘Please tell me this study is biased in some way!’ He enclosed a link to an article that had appeared, on-line, in Medical News Today (never ‘eard of it).

The article headline was ‘Lipitor reduces heart attack and stroke risk for diabetes patients.’ And it referred to a sub-group analysis from the TNT (Treating to New Targets) trial. In this trial people were given either 10mg, or 80mg Lipitor to see what would happen.

The commentary on the trial was provided by Prof James Shepherd (not a medical doctor) from Glasgow, Scotland. He ran the hugely influential West of Scotland  (WOSCOPS) study on pravastatin. He is absolutely pro-statin, and has received vast sums of money from statin manufacturers.

These data are the first to demonstrate the CV benefits of lowering LDL-C beyond recommended guidelines with atorvastatin 80 mg in this high-risk diabetic population. Moreover, patients achieved these results without additional muscle risks,” said James Shepherd, MD, Clinical Academic Consultant, Department of Pathological Biochemistry, University of Glasgow Medical School, Glasgow, UK.

Anyway, returning to the original question ‘Please tell me this study is biased in some way!’ As you can tell, my correspondent is not pro-statin. But at least he was willing to read a report that ran counter to his own views, and he was also willing to accept the findings – if they were valid.

Despite my own views, I too, always try to approach new studies with an open mind. Perhaps I am wrong about statins and cholesterol lowering. Maybe statins are a good thing. Hard as it may be, I attempt to remain objective when faced with data that appears to contradict my own thoughts. But I also look for the flaws.

To return to the study

Data presented at the annual meeting of the ADA have shown that patients with diabetes and coronary heart disease (CHD) on Lipitor who lowered their cholesterol to well below currently recommended levels experienced significantly fewer heart attacks.’ and strokes than those who achieved recommended levels.’ 


Those patients who received atorvastatin 80 mg also experienced 25 percent fewer major cardiovascular events (CHD death, non-fatal heart attacks, resuscitated cardiac arrest, and fatal or non-fatal strokes).

So, is the study biased…..? Wrong question. The question that you need to ask is this? What is missing? What is not said? In most areas of life this is quite a difficult thing to answer. How can you spot something that isn’t there?

Within the arcane world clinical trials, however, the answer is usually simple. When you give a drug e.g. a statin, you are looking for benefits on cardiovascular disease. You are also looking for a reduction in overall mortality.

Therefore, if a trial reports benefits on CV mortality, but not overall mortality, you know absolutely and for certain that there were no benefits on overall mortality i.e. the drug did not save any lives. Sure as eggs is eggs, if there had been a benefit on overall mortality, you would never hear the last of it. In this case, silence speaks volumes.

As I have said to a number of friends, colleagues and fellow doctors over the years. You can only die of one thing. If I ran a clinical trial in which I gave half the people a lethal dose of botulinum toxin, and gave the other half a placebo. I would reduce the rate of death from CV diseases to zero in botulinum group.

I could then claim that botulinum toxin provides complete protection against heart disease, as no-one in this group died of a heart attack. However, the statistics on overall mortality might not look so good.

In a less extreme version, if you give high dose statins to half the population and this prevents death from CV disease……so what, if all you have done is to change what is written on the death certificate, not the date.

To my mind, a successful clinical trial is one in which less people died…period. Not a clinical trial in which you changed the method of dying. So, here is a bit of advice. If a clinical trial does not mention overall mortality it was either unchanged, or made worse. Not much of a sleight of hand really, but it seems to work every time. Sell, sell, sell.

July 14, 2005


By Red Flags Columnist, Dr. Malcolm Kendrick
( email - malcolm@llp.org.uk )  

 The great thing about statins is that, in study after study, they have been shown to have remarkable, life-enhancing effects on all sorts of diseases — other than heart disease. I have kept a rough checklist: statins have beenfound to protect against breast cancer, colorectal cancer, Alzheimer’s, rheumatoid arthritis, diabetes, multiple sclerosis, liver damage and macular degeneration.

When I say found to protect against, I mean sort of. All these wondrous, magical effects have tended to be somewhat less than clear-cut when you look more closely at the research. Basically, you get a few thousand patients on statins and match them against a few thousand people not taking statins. You find that the people on the statins have less breast cancer, colorectal cancer, Alzheimer’s etc.

There are two possible explanations for this (actually there are more, but there are two main possible explanations):

1: Statins protect against these diseases;

2: People put on statins have higher cholesterol levels, and people with higher cholesterol levels are less likely to get the above diseases in the first place. Ergo, the protection‚ has nothing to do with the statins.

As you can imagine, explanation number one is used by the statinators amongst us, and then hyped around the world by the PR machine paid for by statin manufacturers, so that we may all be reassured of the general wonderfulness of statins.

Occasionally, however, the truth will emerge. With regard to dementia, a major prospective trial, done to find out if statins actually do protect against dementia, was published this week. And, surprise, surprise, they don’t.

Conclusions:  In this cohort study, statin therapy was not associated with a decreased risk of dementia. Methodological differences may explain why results of this cohort investigation differ from those of prior case-control studies. Additional investigation is needed to determine whether and for whom statin use may affect dementia risk. (1)

Have you heard of this study? I suspect not. Will you hear much about this study? I suspect not. I like the conclusion that “methodological differences may explain why results of this cohort investigation differ from those of prior case-controlled studies.”

Very polite, guys, very polite indeed. What you mean is that your study was done properly, and the rest were marketing baloney.

This little sliver of truth has been brought to you by redflagsweekly. The only place left in the world, it sometimes seems, where anyone can be bothered to study medical research properly.

  1. Thomas D. Rea et al: Statin Use and the Risk of Incident Dementia, The Cardiovascular Health Study‚ Arch. Neurol. 2005;62:1047-1051.


July 29

Too Little, Too Late

By Red Flags Columnist, Dr. Malcolm Kendrick
( email - malcolm@llp.org.uk )

It has long bothered me that there is a vast library of medical research out there that has become almost completely unreliable. Some time ago, I wrote that I had almost completely lost faith in the use of references, as you could always find as many references as you wanted to support almost any argument you cared to make.

It is also true that many references are based on bogus research that has since been disproven. Added to this, a whole range of papers directly contradict each other. Furthermore, very often the information in the abstract is in conflict with the data you can find in the paper…. I could go on.

In short, the global medical library is a like a computer program full of an unknown number of information “viruses” all replicating away like mad. However, this represents such a huge problem that the medical research establishment has tended to ignore the elephant in the living room, and carry on with polite conversation as if nothing is wrong.

So, it was nice to see the British Medical Journal (BMJ) getting to (slight) grips with the problem this week.

Suspected research fraud: difficulties of getting at the truth

In April 1992, the BMJ published a randomized controlled trial on the effects of dietary intervention to prevent further heart attacks in susceptible patients. One of its key findings was that a year of a low-fat, fibre-rich diet almost halved the risk of death from all causes.

This study went on to become a "citation classic," cited 225 times (at the time of writing), including in guidelines, and its lead author, Dr. Ram B. Singh, went on to publish many papers in other journals.

And Dr. Ram B. Singh made it all up.

And this study nicely highlights another problem. Dr. Ram B. Singh published a paper that supported the current scientific prejudice. Namely, that a high-fat diet causes heart disease. So, no one would have been motivated to question it at the time. If he had tried to publish a paper (like a certain Robert Atkins) claiming that a high-fat diet prevented heart disease, then he would have been hung out to dry.

Actually, as I sit and think about it, my blood starts to boil. There is so much that is wrong. Science relies on a number of things. Accurate, believable information is probably number one. But there is no system in place to provide this. Even now, although that we know Ram B. Singh made up his research, nothing will be done to remove his papers from libraries. Nothing will be done to remove his citations from PubMed.

And how many more Ram B. Singhs are there? We already know that pharmaceutical companies bury negative trials, and re-write papers to make drugs look better than they are…. The more you think about it, the bigger the problem becomes.

Time, I think, to start a movement, which I shall call “The Science Puritans.” We shall start our own database of scientific research. Nothing gets in it until a piece of research has been independently redone, and verified, by another research group. All research shall be grouped together so that positive and negative studies are lined up so that both sides of an argument can be seen. All new papers must mention studies that do not support the current dogma.

If research is found to be false, it will be instantly removed from all databases, and all papers using that research as direct support for their arguments will also be removed. I know what you are thinking. Fat chance. But you know radical action must be taken. Because the system is now almost irredeemably corrupted.


August 3

Temporarily Able

By Red Flags Columnist, Malcolm Kendrick, MD

Some time ago, I was looking through the latest definitions of various states of health. I can’t remember why. I think I was writing a paper on multiple sclerosis and trying to establish the various stages that you may progress through, from fully fit and able to bed bound and incapable of feeding yourself.

All types of health “states” were catalogued for all sorts of diseases. However, the really depressing definition was left to last. Someone with no disease or disability of any sort — the type of person you or I might call “healthy” — was defined as temporarily able. As if health is a strange abnormal state, which, happily, given a bit of time, will revert to the more normal human condition of illness.

For some reason, this memory sprang into my mind when it was announced that the United Kingdom is going to introduce bowel-cancer screening for everyone between the ages of 60 and 70 as part of our new Brave New World of enforced healthiness for all. An announcement that left me profoundly depressed.

Despite my misgivings, however, I have to admit that, in general, most people seem ecstatic about the introduction of yet more health screening. It seems to be a self-evidently good thing. Pick up a disease early, especially cancer, and you can cure it. But if it were left for a few more years, it would be deadly. Who could possibly object to that? Anything that stops people from dying must be a good thing, mustn’t it? Stop being an old curmudgeon.

I don’t know…. Somehow all this screening and monitoring and treating things like raised blood pressure with drugs — for the rest of your life — seems to me to be in danger of stopping people from living, not dying. It may seem trite to say “no one gets out of life alive.” This attitude is often dismissed as defeatist or nihilist. But I think it is critically important how our lives are lived — not just how long they are.

Even from a purely practical perspective, I have doubts. If two million people are sent kits through the post to test for blood in the faeces (how lovely), around five percent will test positive. That is 100,000 positive tests. Around 90 percent of these will be false positive, by which I mean the test will come back positive for a variety of different reasons, not cancer.

So, 90,000 people will be scared witless. (I was going to say *#$tless, but it didn’t seem appropriate.) They will all undergo colonoscopy, an unpleasant and costly procedure, and then be pronounced “healthy” — sort of. Despite this, many of them will become horribly worried and a certain number will suffer chronic anxiety. Believe me; I see them in surgery every day.

If, on the other hand, you decide to throw the kit away in a fit of deranged personal liberty, you will be reminded and chided for years that you really should take the test — it’s for your own good, don’t you know.

I don’t know. There are always those who will say that even if one life is saved, it is worth any price. But I am not so sure. After all, we accept tens of thousands of deaths each year for the convenience of driving cars. Why won’t we accept a few hundred more deaths a year for the freedom of living without added anxiety and fear in our lives?

As readers of Red Flags are probably aware, if you screened everybody for every illness, everybody would be found to have an illness — even if many of these findings would be false positive. And if everyone is ill, then everyone needs treatment of some sort. And I am not sure whether I want to live in a world where we are all considered to be ill, and under the command of the medical profession. For now, I am temporarily able and I would like to stay that way.


September 9

What Tangled Webs We Weave

By Red Flags Columnist, Malcolm Kendrick, MD

Refreshed from a holiday in France, I returned to work to find an e-mail informing me that a German study has concluded that Lipitor (atorvastatin) might not be as effective as the other statins, and might also have more side-effects.

Well, it must be true because it was a study done by the Institut fuer Qualitaet und Wirtschaftslichkeit im Gesundheitswesen. And there is no way on Earth you could argue with an institute as formidable sounding as that. An institute, I picture, entirely populated by white-haired professors all looking like a cross between Albert Einstein and Socrates.

Are they right? Are they wrong? Frankly, I have almost given up all hope of knowing whether research is true or not. When I see medical headlines now, I just think to myself, So what was in it for them? I imagine that the Institut fuer Qualitaet und Wirtschaftslichkeit im Gesundheitswesen is paid by the German government to look at healthcare costs.

Their agenda, therefore, will be to save money for the German health service. Lipitor costs more than the other statins — ergo, the Institut fuer Qualitaet und Wirtschaftslichkeit im Gesundheitswesen will be attempting to prove that it is no better than simvastatin, lovastatain, and others of that ilk.

You see, bias does not just operate in one direction — some of it is anti-drug. And almost no one (maybe that should be no one at all) does disinterested research anymore — especially in the medical field. Everyone, it seems, is trying to prove his or her own deeply held prejudices or make money or both.

I think it was Robert Heinlein who said that the most important two words in science are “that’s funny.” But I think I have given up looking for unexpected results in medical research. Amazingly, almost all research comes up with the expected result. Or if it does not, unexpected results are immediately explained away in a flurry of post-hoc rationalization. “In this study, statins did not reduce mortality but this was because of blah, blah, blah … blah, blah, blah … complicated statistics … blah, blah, blah.”

So, who to believe? What is true? How can we possibly tell anymore? Pfizer has made huge play on Lipitor’s safety and lack of side effects; Merck made huge play on Vioxx’s safety and lack of side effects. Merck, it appears, was suppressing negative data and promoting positive data. Is Pfizer doing the same? Who knows, but since Pfizer pays for most of the studies on Lipitor itself, it could undoubtedly bury any negative results.

Personally, I have almost reached the point where I don’t believe a damned thing. Correction: If I can see that individuals are clearly trying to establish the truth and, in so doing, they are antagonizing vested interests and getting into trouble, then I am much more inclined to believe what they say. The downside of this approach is that you tend to give a little too much credence to crazed loons of the green-ink letter-writing variety.

Better that, however, than giving credence to the honoraratons — a race of opinion leaders whose views can be perfectly manipulated through the payment of large sums of money.


September 14

More Grist To The Mill

By Red Flags Columnist, Malcolm Kendrick, MD

“Recent and soon to be published research reveals that soldiers who fought in theatres as diverse as Vietnam and Lebanon are not only more likely to die from an accident on their return, but are also twice as likely to develop cardiovascular disease, diabetes and even cancer later in life.
— New Scientist, Aug. 27, 2005

For some time now, I have been banging on about the fact that “stress” causes diabetes, heart disease and even cancer. Of course, my definition of stress, or a stressor, is any factor that can lead to a long-lasting dysfunction of the hypothalamic pituitary adrenal axis (HPA-axis). This definition may seem — and probably is — a bit pedantic. But it does have the advantage of being reasonably accurate. That is more than can be said for the word “stress,” which can mean all things to all men.

My pedantic definition also helps to bring together a whole series of seemingly unrelated risk factors for heart disease and diabetes such as: depression, physical trauma, spinal cord injury, use of steroids, smoking and psychological stress. All of which can in some, but not all, individuals lead to HPA-axis dysfunction.

I had always believed, without any supportive evidence it must be said, that soldiers suffering from post traumatic stress disorder (PTSD) would be at greatly increased risk of heart disease and diabetes — primarily because PTSD is characterized by a low cortisol level, which points directly at an HPA-axis dysfunction. (See previous columns for clearer explanation.) Up to now, there was no evidence linking PTSD to diabetes and heart disease. Now there is.

Changing tack slightly, I tend to believe that the best test of any hypothesis is whether it is capable of predicting findings, or events. Once something has happened, it is always possible to come up with some explanation as to why it happened. This type of science is normally called economics, a science that can inevitably tell you why something took place — e.g., the Great Depression — but can never actually tell you what is going to happen hereafter  — e.g., the next Great Depression. This is why economics has been dubbed the dismal science, requiring copious use of a “retrospectoscope.”

Equally, in the world of heart disease, everyone can give you an explanation of why rates of heart disease went up, then down, in various parts of the world. And why this all fits perfectly with established dogma — even when it clearly doesn’t.

However, emboldened by research on soldiers and PTSD, I will stick my neck out and make a few predictions about the future rates of heart disease in various populations around the world. (Please print off this article, put it in a sealed container and open it in 50 years — then honor me posthumously with a Nobel Prize.)

  • The rate of heart disease in former Eastern European countries — e.g., Lithuania, Poland, Latvia, Slovenia, Croatia — will fall and continue to fall for the next 30 years. (Assuming Russia doesn’t invade again.)
  • The rate of heart disease in troops sent to Iraq will rise sharply.
  • The rate of heart disease in China will rise rapidly over the next 40 years. (Unless their economy collapses, which could, of course, lead to major social problems.)
  • The rate of heart disease in Mexico will become the highest in the world.
  • In the U.S., the rate of heart disease in immigrants at the lower end of the social scale will become very high.
  • Survivors of Hurricane Katrina will end up with high rates of heart disease.
  • Rates of heart disease in the U.S., amongst Caucasians, will continue to fall.

In general, my prediction is that stable populations will see rates of heart disease fall. Unstable populations, and traumatized populations, will continue to see rates rise. What I cannot predict for certain is which populations will remain stable and untraumatized. However, this latest study of combat troops once again demonstrates that heart disease is primarily a disease triggered by underlying psychological trauma, creating a real and measurable physiological upset.


September 28

The Constant Gardener 

By Red Flags Columnist, Malcolm Kendrick, MD

Some of you may observe the actions of the pharmaceutical industry and wonder why, from a PR perspective, it seems intent on taking dead aim somewhere between the second and third metacarpals (bones in the feet, in case you were wondering), then determinedly pulling the trigger. Not once, but time and time again. To quote Arnold Schwarzenegger in the movie The Terminator, “I use an Uzi nine millimetre.”

It is almost impossible to think of an industry that displays itself in a worse light. A few years back, when British authorities turned down Relenza (anti-flu drug from GlaxoSmithKline), GSK’s then chairman, Richard Sykes, threatened to close down the entire R&D and manufacturing facility in the U.K. and move elsewhere. I am not sure, but I think he achieved the world record for hurling the greatest number of toys out of his pram at the same time. He definitely got the distance record.

Whenever you read the press nowadays, it seems that yet another pharmaceutical company is being sued for mis-selling products to doctors, fixing prices, firing whistleblowers or bribing politicians. Or, most serious of all, suppressing information about the dangers of drugs. Vioxx being the best current example.

Much of what goes on, of course, never even breaks surface. A few years ago, a friend was telling me of an interesting experience. He works for the New Zealand company Adis International, a group that is quite academic and produces a number of scientific papers and journals, one of which is called Drugs. This is a semi-autonomous publication, distributed to doctors, which provides in-depth information on new drugs. Whether or not anyone ever reads it is a moot point.

Despite the fact that Adis publishes Drugs without sponsorship, the reality is that it covers its costs, plus profit, by getting pharmaceutical companies to purchase hundreds of thousands of reprints to dish out at international conferences and suchlike. So Adis, like most medical publishers now, can come under considerable pressure to present drugs in a favourable light. Lest they lose the lucrative reprint fee.

Sorry about the long preamble, but this story makes no sense without it. Anyway, Adis did a Drugs edition on Baycol (cerivastatin), which mentioned that if you gave Baycol in conjunction with a fibrate (another cholesterol-lowering drug), there was a greatly increased risk of causing rhabdomyolysis (severe muscle breakdown, sometimes fatal).

Bayer, the manufacturers of Baycol, did not want this information published. The company felt it may have an impact on sales, and threatened to cancel its reprint order — worth hundreds of thousands of dollars. Adis, to its credit, did not back down, and lost a lot of money, although Bayer did take up its original order.

In a supreme irony, as often happens, Baycol was withdrawn from the market (due to the fact that it killed lots of people through rhabdomyolsis). However, as part of its defence, Bayer then waved the Drugs issue about, making the point that it had always been up front about the risks of rhabdomyolysis, and were thus a highly ethical company. One never knows whether to laugh or cry at such effortless hypocrisy — or should that be sheer effrontery.

Despite hundreds of such examples (perhaps you would enjoy being regaled with a few more), if you read the pharmaceutical industry press — as I do — you will never see the slightest recognition that perhaps, just perhaps, the industry may possibly be the teensiest weensiest bit responsible for its image. In the industry’s eyes, its tarnished reputation is all the fault of deranged, anti-capitalist, anti-globalization, lefty, pseudo-communist-quasi-anarchists. (They must be talking about me.)

But why do they act as they do? I believe that the driving force behind their actions is that pharmaceutical companies have become the darlings of the stock market and feel that they should act accordingly. I read somewhere that U.S.-listed pharmaceutical companies make more pure profit than any other industry in the Fortune 500. They are the big hitters, the ROI (return on investment) kings, the steroid-pumped über-capitalists.

In this world, a failure to achieve double-digit growth year after year is seen as wimpy. In this world, CEOs are chosen for their ability to wring the last drop of profit out of every drug launched. They, in turn, are utterly share-price-driven, and this attitude infects the entire workforce.

Squeezed by the pressure to reinforce financial success, the industry has become a treadmill where everyone, from the CEO to the most junior sales representative, has to run faster and faster to satisfy the voracious appetite of the shareholders (people like you and me).

This is a built-in problem with capitalism recognized, in part, by Karl Marx, no less.

“For as long as a capitalist intends to stay in business, he must exploit his workers to the legal limit. Whether wracked by guilt or not, the capitalist must act as a ruthless exploiter. Similarly the worker must take the best job on offer; there is simply no other sane option. But by doing this we reinforce the very structures that oppress us.” K. Marx

I would add to that statement. “For as long as a capitalist intends to stay in business he must exploit his worker … and the Government, the legal system — and any other factor that impacts upon his business. Whether wracked by guilt or not, the capitalist must act as a ruthless exploiter.” M. Kendrick

I don’t suppose too many CEOs are wracked by guilt about their actions. But even if they were, how could they act in any other way? If they were to put ethics above profit, profit would inevitably fall, and they would be gone — cast aside by brute desires of the stock market.

They must exploit every situation to its full advantage. Whether it be carrying out dodgy drug trials in Africa, subtly (or not so subtly) suppressing information, becoming buddies with the FDA or providing significant financial rewards to various “friends,” this is all part of how winners, win.

In most industries, when winners win and competitors are crushed, the fallout is not that serious. Maybe we all drive an inferior car, or end up with VHS rather than Betamax, or Microsoft rather than all the other operating systems in the world that are far better. However, when pharmaceutical companies win, the fallout can be deadly. As we have seen.

But, as I have said before, and will continue to say, the problem does not lie with individual actions, or individual companies. The problem is inherent to capitalism, the unfettered free market. In the end, if you put profit before anything else, then profit is what you will get. And you cannot expect individual pharmaceutical companies to take the moral high ground. They can’t afford to, even if they might like to.

Capitalism, like any other ism from socialism to environmentalism to animal rights(ism), has good bits and bad bits. And like any other ism, when uncontrolled, it becomes extremism, and extremism is always a disaster for humanity.

End of sermon.


October 19

ASCOT–BPLA (Another Stupid Commercially Overhyped Trial – Before Prescribing Look Again)

I have been aware of the ASCOT study for some time. In fact, it seems to have been spewing out results for the past 500 years or so. Maybe not quite that long but, boy, it sometimes seems like it.

First we had ASCOT–LLA (Anglo Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm). This was stopped early because of the fantastic benefits of giving people a statin. So great were the benefits that it was considered unethical for the trial to continue. The difference in overall mortality between the two arms of the study was a majestic, gigantic … zero.

But don’t be silly, overall mortality wasn’t what the study was designed to show. It had been set up just to look at cardiovascular mortality. And the benefits here were…? Listen up and stop asking difficult questions.

More recently, we had the ASCOT–BPLA. In case you didn’t know, BPLA stands for Blood Pressure Lowering Arm. This study claims to have proved that the newer, and naturally far more expensive, blood-pressure-lowering tablets are better than such older, cheaper ones as beta-blockers and diuretics.

Of course, this study, too, was stopped early due to fantastic benefits — this time in overall mortality? How they managed to work this out is an interesting question as the study was never designed — or powered — to measure this end-point. But these heroic researchers managed it, and they even gave the reduction in risk a precise statistical probability. (You may not find that funny, but I do. However, a joke explained is a joke ruined, I always say.)

Thus, once again, another part of the ASCOT trial has been hailed as a glittering triumph. A triumph, in my opinion, of mangled scientific methodology because the end-points that the study set out to measure were non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). Not overall mortality, or stroke, or combined cardiovascular end-points — which is what all the noise has been about.

You may ask why they chose these two rather strange sounding end-points. Frankly, God knows, I have given up trying to work it out. In fact, one of the reasons I have not commented on this study before is that I have found it almost impossible to understand why they did it, or what they expected it to show. This is despite reading the protocol about 50 times. Maybe you could read it and let me know. There is an entire mind-boggling ASCOT website at the following address. http://www.ascotstudy.org/healthcare_professionals/index.htm

Anyway, back to my main point. In ASCO–BPLA, the primary end-points were non-fatal MI and fatal CHD, and the study showed no benefit on either. Somehow despite this, it has been hailed as an unrivalled success — a study that will change the face of hypertension treatment or some other such grandiose claim.

So you see, If you set your mind to it, you can get your study to prove anything you like. To hell with the facts. Decide what answer you want, then go get it. Let not science stand in your way. “Researchers, these days, do not seek; they find,” in the words of Pablo Picasso.

The reality of the ASCOT–BPLA study is that it has laid waste to scientific methodology. You may care to read some of the criticism of the study on the British Medical Journal’s rapid response pages.  http://bmj.bmjjournals.com/cgi/eletters/331/7521/859?ehom

But, in the end, you can criticize all you like. You will never stand in the way of the new drugs. Resistance is useless. For it has been decreed by the hypertension opinion leaders, whose future earnings and prestige are closely linked to their buddies in the pharmaceutical industry, that newer (costly, still-in-patent) blood-pressure-lowering drugs are to be used. Several major trials, such as ALLHAT, (Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial) proved this was not true. So they were remorselessly attacked, their methodology shredded, and then ignored.

Now we have a trial that showed almost nothing — with a methodology so twisted you could use the trial protocol to pull corks out of wine bottles — and it is hailed as marking a sea change in the treatment of high blood pressure.

Nothing, it seems, can stop the drive toward more expensive blood-pressure-lowering drugs. Negative trials are pulverized and left for dead. Studies like ASCOT–BPLA have their protocols altered mid-stream (I kid you not) and are then subject to wild post-hoc speculation. Somehow, I am reminded of a film starring Arnold Schwarzenegger.

Listen! And understand. That pharmaceutical industry is out there! It can't be bargained with. It can't be reasoned with. It doesn't feel pity, or remorse, or fear, and it absolutely will not stop! Ever! Until you are dead!

Keep taking the tablets.


October 24

Reflections On Scientific Dogma 

The Nobel Assembly at Karolinska Institutet has today decided to award

The Nobel Prize in Physiology or Medicine for 2005

jointly to

Barry J. Marshall and J. Robin Warren

for their discovery of

"the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease"

It was good to see these two winning the Nobel Prize, with the key piece of following text appended.

This year's Nobel Prize in Physiology or Medicine goes to Barry Marshall and Robin Warren, who with tenacity and a prepared mind challenged prevailing dogmas.

“Who with tenacity and a prepared mind challenged prevailing dogmas….” A few short words. As if the Second World War could be encapsulated thus, “In the Second World War, the Allies defeated Germany, Japan and a few other countries after a series of successful engagements.”

I followed the helicobacter story from pretty early on in the proceedings. At first, Barry Marshall and Robin Warren were personally attacked and ritually humiliated for questioning the wisdom of their superiors. When this didn’t have the desired effect, their work was rubbished. Barry Marshal, at one point, was forced to swallow helicobacter pylori himself, then develop ulcers, in order to prove that bacteria could cause ulcers.

As the work of these two became better known, and appeared to be threatening the multi-billion-dollar market in ulcer-healing drugs, the major pharmaceutical companies lined up expert after expert after opinion leader to intensify the attack. It would have been easy to fold under this level of pressure. Good on Marshall and Warren for sticking to their guns.

Their story highlights an issue about science that has bothered me for years. Namely, the incredible, stifling power of dogma. One would hope that scientists have open minds, but the more you study science, and scientific thinking, the more it becomes clear that the minds of most scientists remain firmly, and highly aggressively, shut.

I have tried to train myself to put all ideas into one of three places — probable, possible or unlikely — and never to allow myself to become emotionally attached to any hypothesis. But most scientists, especially medical scientists, seem only to have two places to store their thoughts. They are true or false; right or wrong; sensible or stupid. This is usually supported by the killer scientific argument, “Do you know who I am, young man?” This is knows as Eminence-Based Medicine.

As we know now, when it came to bacteria living in the stomach, the prevailing dogma was that no bacteria could live in such a highly acidic environment. On the face of it, this seems quite a sensible thought. I think I probably believed it to be true myself. It just happens to be utterly wrong.

Scientists also argued that sunlight was essential for the development of life — until whole colonies of plants and animals were found living next to volcanic vents thousands of feet under the sea.

I communicated for a time with Thomas Gold, a geologist, who argued that the surface of the Earth floated about on tectonic plates. He was flung out of various geological conferences in the late-1950s, along with anyone else daring to propose this madcap idea. (Read the literature today and you get the impression that this theory just gently evolved under the benign gaze of wise geological opinion leaders…. Not so, this was a vicious battle.)

Last year, I spent some time looking into the history of surgery for breast cancer. For about 80 years or so, the dogma was that surgery should remove as many lymph nodes, and as much of the breast and surrounding tissue, as possible. This was the so-called radical mastectomy. To argue otherwise was to be hurled from the bosom of a surgical society — as happened to several brave souls. The thinking behind the radical mastectomy was, of course, utterly, and disfiguringly, wrong.

At one time, if a patient had a heart attack, it clearly made sense that he should spend eight weeks in strict bed rest to protect the heart from strain, or some other such superficial and stupid nonsense. During astronaut training, it was discovered that six weeks of bed rest was horribly damaging to the heart. And so the bed rest idea was itself put to rest. Quite how many hundreds of thousands of people were killed by enforced bed rest will, I am sure, never be known.

I could go on and on. These are just the examples that spring most readily to mind. Perhaps this is the nature of scientific endeavour. Only those few brave individuals with the energy and sheer bloody-mindedness will break through prevailing dogmas to move science forward. Whilst the “opinion leaders” effortlessly crush the other 99 percent under the jackboot of prevailing thought.

If I had just one wish, it would be this: that all scientists took the following oath. “I shall always support and encourage new ideas, no matter how superficially idiotic and wrong they may seem. I shall also remember that established and comfortable ideas may well be wrong, and should be attacked and criticized at all times.”

The chances of this happening are, officially, fat.

PS:  A raised cholesterol level causes heart disease. Ho, ho, ho.


October 28

Justice Saves Lives  

There are few things that enrage us quite so much as a sense of injustice. There is nothing, for example, so anguished as the embittered cry of a five-year-old, “That’s not fair.” My usual reply to such a statement is that when you emerge from the womb, there isn’t a banner at the end of the bed stating, “Don’t worry, life will be fair.” Quite the opposite, in fact. So get used to it — and learn to play the game.

To be truthful, however, despite my carapace of cynicism, there is nothing that winds me up so much as unfairness. Be it someone barging to the front of a queue, or getting rewarded by claiming credit for something they haven’t done. And such a sense of unfairness, or injustice, can burn away inside. It is an unpleasant feeling and, intuitively, I can sense that it probably isn’t good for me to allow such feelings to persist.

Now evidence has emerged that unfairness, or injustice, can actually cause heart disease.

A study of 6,442 British male civil servants measured the extent to which they experienced "justice at work." Two questionnaire tests conducted in the 1980s were followed up by recording cases of heart disease in the group between 1990 and 1999. Heart disease incidence in men who reported a high level of justice was almost a third lower than it was in those who believed they were less fairly treated…. An earlier study had shown that office workers had lower blood pressure on days spent working with a supervisor they perceived as fair.”

For those who have read my ramblings on a regular basis, and my oft-stated view that chronic stress is the primary cause of heart disease, my interest in this study should come as no surprise. But it is always nice to see such clear-cut support.

And I rather enjoyed, as well, the conclusions of the authors:

The authors concluded it was plausible to link a high sense of justice with a reduction in chronic stress, which in turn lowered the risk of heart disease.
“Just treatment may communicate status and value, whereas lack of justice may be a source of oppression, deprivation, and stress,” they wrote.
“Justice, equity and altruism have been the drivers of benign developments in human societies according to a wide range of studies across a broad spectrum of disciplines.”

So, there you have it. More proof, if more proof were needed, that we humans are rather sensitive souls. If you upset our brains, and create a sense of oppression and stress, our brains will then kill us. For an exact mechanism of how this works, read my next article.



More essays by Malcolm Kendrick