h2g2 The Hitchhiker's Guide to the Galaxy: Earth Edition

>Note also that Aspirin would struggle to get past the hurdles of safety for science based medicine if it were only being discovered today.
It is no longer acceptable to use it on children because of the risks to health.

But it does have it origins in traditional remedies. Which only serves to highlight the flaws in trusting to traditional remedies.
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I'd be interested to get your take on this Dr. Zen.

I'm quite interested in the specific risk to children as opposed to other pain killers, because of course all drugs carry risk.

And what is your opinion of drugs, which may or may not have their origins in traditional medicine, and therefore what conclusions we may then draw about traditional medicines?

I'm going to answer Yelbarks points first, and then Effers in a separate post - they make quite different points.

What is a Science based Health care intervention? - I would say that it is one that can be shown to be effective, in a measurable way. This could be a number of things:

- The use of acetylsalicylic acid to relieve pain, and prevent heart disease. This works inhibiting the COX pathway that produces prostagladins.
Whether you get the acetylsalicylic acid from Asprin or from willow bark, it still works in the same way and has an effect on the body.

- The use of Cognitive Behavioural Therapy for the treatment of anxiety and depression. That's been shown to work as effectively or more effectively than antidepressants.

- The use of physiotherapy to improve mobility after a stroke.

- The use of a diet low in phenylalanine to prevent serious complications in the genetic disorder phenylketonuria.

These are interventions that work and have measurable effect on the body. The effects of a treatment are examined scientifically and the treatment is modified based on science. It's not about using a method that has been handed down over centuries, but rather a method that has been shown by science to work. When more scientific evidence becomes available then the treatment should be modified.

It doesn't matter so much how a treatment works, rather that it does work. Sometimes an effective treatment is found and then years later a mechanism is discovered. Sometimes we find the mechanism that needs modifying and then design a treatment.



Time and again homeopathy has been shown to work no better than placebo. But all medical interventions have been shown to work better than placebo. So therefore homeopathy must not work as well as medical interventions. Or it would be effective.

There are many reasons why you might think that homeopathy / placebo works, you might have got better on your own anyway. You might feel better because you are enjoying the attention, or because you want to take control of you condition. If you look at how homeopathy claims to work you can see it is very unlikely to work at all.

First you take a very small amount of a substance,

Then you dilute it several times, to the point where their is not likely to be one molecule of the active substance left in the water.
Then you bash the water 12 times against a leather bible.

No wonder it doesn't work any better than water. It is water. The idea that water has memory is rather silly. How on earth can water remember the substance that it was meant to remember without it remembering all the excrement that was in it.

But if you showed me convincing evidence that it works then I will start to prescribe it.



The overuse of antibiotics is not an argument in favour of the use of alternative medicine. In fact the prescription of antibiotics for a cold is about as logical as the use of homeopathy for the induction of labour. Neither of them work.

http://www2.cochrane.org/reviews/en/ab003399.html



As for 'Chi' immeasurable energy and the power of spirits. Well you can't prove that they don't exist, in much the same way that you can't prove that there isn't a giant invisible teapot orbiting the earth. You can only detect something if it has an effect on something else, and many proponents of energy healing claim that it has an effect on the body.

But you can examine whether they have a healing effect on the body, you would have to come up with some way of comparing them to a placebo intervention. You could test healers who claim to be able to detect an energy field to see if it they could detect one from the other side of the screen.

The short answer is Reye's Syndrome.

The long answer is currently on a notepad file on my desktop.

That last post was actually a simipost with Effers post. So I'm going to answer her post in a separate one.

You can discover drugs by knowing the mechanism of design and designing a drug that is likely to affect it. So If I wanted to find a drug that would be effective against angina, and I knew that the beta receptors on the heart were overstimulated in angina, I could find out more about the structure of the beta receptors, and using that knowledge design a drug to block them. I would test the drug to see if it was effective, and eventually get it to market. I am going to call that way of designing a drug 'forwards'.

On the other hand I may notice that the Wawiga tribe of Peru has always used the bark of the Mau Mau tree to treat pain. So I could look at the bark of the Mau Mau tree, test it, find out the most effective preparation, the optimal dose, and then conduct a trial to see if it was effective. Other scientists would then want to find out 'how' it worked, because it would be an good way of finding out more about the body. They may find out how it worked, or they may not find out how it worked. But either way that would not affect the fact that it worked. I would call this method of drug discovery 'backwards'

I love stories of backwards drug discovery, and I find them totally fascinating. But because a herb has been shown to contain an active ingredient doesn't mean that it's a validation of all herbal medicine, or even all alternative medicine. Once something is found to be effective it falls into the remit of 'medicine', not alternative medicine. I think that looking into various traditional medicines from around the word would be a great way of finding new drugs.



The use of Aspirin in children.

The decision about whether a drug is safe for a particular use is a complex one ha involves balancing the risks and the benefits of that drug, and whether there are any alternatives available. It involves a lot of complicated mathematical modelling. It seems a sensible decision to me, but I don't have access to all their data.

Aspirin was used to reduce temperature and pain in children. There are two other drugs that do a similar job just as effectively: paracetamol, and Ibuprofen. Usually the use of them is to make the fever more tolerable, not to actually save lives, or reduce the duration of the illness. So you have three drugs that all do a similar jobs.

One of the drugs was found to be associated with a rare but serious condition, called Reyes Syndrome. This kills children. The other two drugs, which do the same job for the same cost weren't associated with a condition that kills children, not very often, but occasionally. Given that there were two other drugs on the market that were equally effective, and also had less side effects it was recommended that aspirin was not given to children under 16.

Thanks Dr. Zen. What you say about something falling into the remit of 'medicine' once its been found to be effective makes total sense. Its origins are irrelevant. Of course it will then be subject to proper scientific testing and trial, to examine cost/benefits, which yes can be quite complex, I understand that. Cost/benefit has to take account of so many factors.

I didn't understand the connection between Jack's statements,

>But it does have it origins in traditional remedies. Which only serves to highlight the flaws in trusting to traditional remedies. <

On the one hand we have *origins* of a medicine. And on the other the idea of the *flaws in trusting to traditional remedies*.

I just couldn't see the connection between the two sentences. To me they are separate ideas entirely.

And thanks for explaining the use of aspirin in children, and its specific risks, and the fact that alternatives are available which don't carry the same risk.

To Jack Warlock-Bacon,

I have read the file of the OP by now, so I know a bit more about "what is making the rounds". It appears that Official Britain wants to treat Alternative Medicine the same as medicine based on the scientific method. I agree that this is ultimately the same process as trying to teach creation as an equal alternative to evolution in school. Neither of which I would be happy with.

To Dr Zen,

that tea-pot analogy is quite striking, I like it. I also like your definition of science based health intervention. As to why my sugar pills might help me fight my hay fever, your explanations are appreciated. - As an aside: One of our cats has been diagnosed with cancer. The specialist who would administer the chemo was on vacation at that time and our home vet suggested some homeopathic stuff to bridge the time until the specialist returned. By the time we had her at the specialist's ultrasonography, the tumors in her liver had considerably decreased. Due to the homeopathic stuff? Who knows? Liver cancer in cats can be fought be cats quite well if they are otherwise in good shape. Giving her those pills with lots of extra yummie food, giving her all that extra attention, treating her extra kindly - all that might have helped get her in good enough shape to help her fight the cancer. And yes, citing one case (where cause and effect are less than clear) does not constitute anything prooflike. I am happy for Ginny, the cat, though. (And we keep giving her chemo, of course).

Anyway, this thread is quite interesting.

Y.

>You can discover drugs by knowing the mechanism of design and designing a drug that is likely to affect it.<


As someone who knows a fairly significant amount about pharmaceutical chemistry I think it important not to over egg this one too much. As far as I'm aware nobody has ever actually managed to do this. Nearly all mass marketed drugs are discovered by mass screens against a disease - rational design is only cited in two cases of marketed drugs and neither of those are active against the disease they were designed against.

Yelbakk,

I presume you know wher the tea pot analogy comes from...

http://en.wikipedia.org/wiki/Russell's_teapot

3Dots,

I do know whence the tea pot hails. In fact, "Tea Pot Atheist" was my tag line for quite a while. The more disturbing I found it when I realized... when I was made to realize that my own post about 'how would you know there is a magnetic field when you don't have the tools to measure it' was in fact an example of the kind of thinking that the tea-pottery ridicules...

Y.

Hi Orcus.

Thanks for enlightening me on the discovery of drugs. So when the drugs Angiotension recpetor blockers such as losartan were discovered how did they go about it.

I would have though that the drug company knew that blocking the angiotensin receptor would be a good way of reducing Blood Pressure, so then went and found a chemical that would do that. Doesn't it work like that? How does it work, I'm really interested in this!

Well I don't know exactly how that particular drug was discovered but generally it will go something like this.

The screen:

Set up a screen against the angiotensin receptor. This will measure the output of that receptor somehow - the assay must be *fast* to allow high throughput and sensitive.

They then will pass every single chemical compound they can lay their hands on - which will be probably millions of compounds - through this assay and see which ones cause the effect they wish (e.g. antagonists will block the receptor - agonists will cause it to do its thing).

These hits will then be analysed for trends and any already-known problems.

The hits will then be chemically altered by the black-art of medicinal chemistry which is to improve such things as pharco-kinetics, reduced toxicty, improve bioavailability and also to increase their activity against the target receptor. All of these things are *very* difficult (nigh impossible) to rationally design from the start.

Typically a 1000 hits might become 5 lead compounds from such a round of redesign and testing. These then go on to clinical trials.

Those 5 compounds will maybe narrow down to 1 (or most often zero) that is actually good enough to be a drug at very end of this process - which typically takes 15 years and hundreds of millions of $$$ or so to complete.



The idea of rational design is to get rid of the mass screen step and try and design a drug through a variety of methods including computational modelling of the binding pockets of the receptor/disease target molecule.
This is extremely difficult to actually achieve in reality although drug companies have certainly been using such methodology for a long time. It has to be said though that you really do need to know the structure of your target - and even this is often no known well enough.
The trouble is that this will miss molecules that agonise/antagonise the receptor in a way that we do not expect. Also, just because you've designed and synthesised a good agonist of your receptor it does not mean it will be any good at actually treating the disease/condition you intended.

Consequently, you can keep this compound in your library and include it in your screens. Lo and behold, it is a good compound for something else and you can market it as a 'rationally designed drug'
Even though it isn't really.

I may be behind the times though, I'm not a medicinal chemist with my ear to the ground of the industry. Last I hear there were two clear examples of rationally designed drugs - dorzolamide and imatinib and both were of the kind of 'rational design' I mention in the previous paragraph - this is pretty well known in organic chemistry academic circles although it's anecdotal in nature, I can't point you to a paper which will say this and the web will tell you they *were* rationally designed...

Orcus, that's really interesting. Although there's a mass screen they do use the knowledge of physiology (eg the existance of an angiotensin receptor) as a starting point. I think that there are a number of rationally designed chemotherapy agents around, I heard that Glevec for Ovarian cancer was, but I can't be sure.

Hi Yelbakk - I'm really glad that this is something you're thinking about.

If you find that homopathy helps with hayfever then that's great. Carry on with it. I suspect it doesn't make much difference, given that Hayfever is something that often gets better on it's own. But if it causes less side effects they why not take it. The aim of treatment for hayfever. is to reduce your symptoms as opposed to cure you disease, so if you find placebo helps then great.

I'm interesting to know more about your cat. She was diagnosed with cancer by one vet, and then given homopathy whilst you waited for a specialist. And the tumours decreased before the chemotherapy, with just the homopathy? Or did it get better with homeopathy and chemotherapy?

If homopathy really is effective against cancer in cats then someone should do a study on it. NOW! it means that water may have memory which would change the definations of physics. It would be much easier to do a study on cats than people - there would be much less paperwork.

If the cancer got better with the homopathy alone, and not the chemotherapy then their could be a number of explanations besides the fact that homeopathy is effecitve.

The cancer could have been misdiagnosed in the first place. Or the orginal vet may have mis-measured the size of the tumours. Ultrasound is rather operator dependent, and someone who does ultrasounds on unborn babies wouldn't be able to manage to do one on the carotid artery in the neck. I'd expect that a vet would need to be competent in the ultrasound of all animals, which may make them more likely to make mistakes. Or it may be that the week of cuddles and extra special food was actually helpful.

It's well known that animals who are stroked get better outcomes. In fact I know of one lab where they couldn't work out why the rabbits on the bottom shelf got better faster than the rabbits on the top shelf. Then they noticed that there was a short lab assistant who would pet the rabbits on the bottom shelf, but couldn't reach the top shelf. Solution - rotate the cages so that they all got a turn at being petted, and low and behold they all got better at a similar rate.

If I am being more cynical it could be that the vet gave the cat the homeopathy because to stop you panicking about the delay in the start of chemotherapy.

BTW the pedat in my feels obliged to point that Asprin is still given to children in very rare circumstances, where their is no alternative drug. Rheumatic Fever and Kawasaki Disease, and Juvenille Stroke are the ones that come to mind.

Gleevec = imatinib

It is one of the two famous 'rationally designed' drugs which are not active against the diseases they were rationally designed for.

That serves me right for not-googling!

Is Kawasaki disease that one where they have a strange fixation for motorbikes?

Sadly not.

On Ginny, the Cat

Ginny was diagnosed with cancer by one vet. She had been very tired, sleeping all the time, not responding to her favorite (or any) food, so the Lady of the Mice (my wife, that is) took her to the vet, thinking she might have some sort of infection. But the vet found nothing until a blood test showed that one of the parameters (white cells? Red cells?) was WAY off. That was when they first suspected leukemia. But when the blood report was sent to an expert, the expert figured that thin one run-away parameter did not indicate leukemia and suggested more testing.
That was when the vet did the ultrasonography and found that the liver, the spleen and both kidneys were very much eaten up by tumors. The pictures are on file. It was that day that we started the homeopathic deal - the appointment with the cancer specialist was three weeks later.
At that specialist, however, the tumors in the liver and the spleen had shrunk (receded? grown smaller?) considerably. They are still there, but smaller (and fewer? Note the question mark).
The tumors in the livers had not changed, neither grown nor shrunk.
Since then, Ginny has received two shots of chemo (vincristine, three weeks apart) and two shots of prednisolone (three weeks apart).
Next time (three weeks from last Tuesday), there will be another blood test plus ultrasonography.

So... what we have seen is that the tumors in the liver and spleen (as documented by vet A) have shrunk after about three weeks (as documented by vet B). During these three weeks, homeopathic treatment was administered. Whether it was the sugar pill (here in fact in an aquaeous solution) or not, I don't know. As I said, both vet A and B did say that cats are pretty good at fighting this kind of cancer when they are otherwise in good shape. All this extra attention certainly did Ginny good. Within these three weeks she has changed from somewhat shy to very (with a capital V) lively and, as far as we can tell, happy.

So in fact all the things you pointed out, Dr Zen, could have played a part. (And if the vet only suggested the sugar pill water to calm *us* - well, it did work. Calm pet owners are better for their pets than worried pet owners. Of course, the vet might have achieved something similar by harnessing the powers of good spirits Only, of course, the Lady of the Mice and I do not believe in *that* kind of nonsense...)

+++ have to finish here --- job is calling +++
Y.

Aren't some alternative treatments really supplementary treatments?

Well, complimentary is better than alternative, because at least you are getting some real medicine to match.

I give you
Dara O Briain (Balance): http://scienceblogs.com/pharyngula/2009/07/in_the_name_of_balance.php
and
Tim Minchin (Storm): http://scienceblogs.com/pharyngula/2009/01/minchin_on_youtube.php

TRiG.