Thursday, August 31, 2006

False teeth and Constipation

Today was another Kings College Hospital day. This involves a total of five hours on the train, and today because of signal failure, a goods train stuck in the station and the failure of a door to open I was 30 minutes late arriving. I amused myself by working my way through Carol Vorderman's Massive Sudoku book. I don't know whether this Japanese craze has reached the rest of the world, but it passes the time.

For those who do not know, Carol, who is a nice looking lass in her forties presents an afternoon television program called Countdown. It has a simple format: competitors are given 30 seconds to find the longest word they can from 9 random letters (though they may specify the number of vowels there are within the 9). A mathematical variation has a selection of 6 numbers which must be added, subtracted, multiplied or divided to make a three figure total that is randomly generated.

This program runs for 45 minutes every afternoon and it is what retirement holds for millions of Britons. The giveaway is in the advertisements that interrupt the program. Glue to stop your false teeth shifting, constipation cures, stair lifts (you probably call them elevators), electric arm chairs that enable the weak to stand up, insurance companies offering ways of freeing up the equity in your house, walk in baths, devices for getting you out of the bath, anti-aging face cream; these are some of the products targeted at this audience.

Carol is an Oxford graduate who was paired with Richard Whitely, an oversized ex-local TV reporter noted for ostentatious jackets. Both got a third at Oxford, which is a sort of degree given to people who go to University determined to have a good time and not do any work. Sadly, Richard died last year. he has been replaced by Des Lynham, a pensioned off sports reporter who is the epitome of 'laid-back'.

After the ward round I had to rush off to be interviewed by BBC radio about the TeGenero affair. The week beginning September 24th is when it all breaks. There will be a Sunday Times article and radio and TV programs about it. Somebody will want a lot of compensation for the experiment that went wrong and somehow they will want to sue the one with the biggest purse (the taxpayer).

The up to date information on the experiment goes like this: the idea was to develop an antibody that would stimulate T cells. There are several disease where T cells are sleeping - AIDS is one and CLL is another. Normally anti-CD28 will only stimulate T cells if CD3 is also stimulated, but TeGenero discovered an antibody that would stimulate T cells all by itself. As they tested it they discovered that it seemed to stimulate regulatory T cells more than ordinary T cells. Regulatory T cells suppress the immune response and would be useful in autoimmune diseases like rheumatoid arthritis and diabetes.

Tegenero was in a quandary. Would their antibody stimulate ordinary T cells, and therefore be useful in CLL and AIDS or would it primarily stimulate regulatory T cells and switch of the immune response, making CLL worse? They tested it in monkeys where it didn't have much effect and from those studies chose a dose that ought to be safe. Because it had the potential to make either CLL or rheumatoid arthritis worse, they decided to test it in normal individuals at what they thought from the animal studies was a very low dose, expecting no effect in man, except minor changes in blood cell populations which would give an indication of which way it would act.

It turned out to be much more active than they had anticipated. Their strategy turned out to be flawed. They compounded the problem by treating 6 individuals with only minutes between them.

There will be several new recommendations from the MHRA which should stop such a disaster happening again. I think the core of the problem is the time that the MHRA is expected to turn around very complex applications. There is not enough time to consult appropriate experts.


Anonymous said...

If memory serves me correctly, TeGenero calculated that, to be on the safe side, the dose administered was 1/500th of the expected clinical dose. Obviously, even this small of a dose caused an extreme immune reaction, with activated T cells brewing up was described as a "cytokine storm," which I suppose is a bit worse than a thunderstorm.

Mistakes happen, though this was totally unexpected. Obviously the immune response was not a dampening of the immune system.

Might make a dandy poison, what? I wonder if a tox screen would pick this up. Probably not.

Maybe will see a similar idea on a crime show one day. After all, they are running out of clever ways to dispatch people.

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