Comment by refurb | Hacker News Reader

Comment by refurb | Hacker News Reader

Wow, that article was a little annoying.

Correct me if I'm wrong, but I get the impression that he thinks our current approach to science is wrong due to our tendency to attribute cause and effect to things where we have no conclusive proof of cause and effect?

Well, if he has a better suggestion on how to approach research, I'm all ears!

First off, I don't think ANYONE who was involved with the development of torcetrapib thought it was a "slam dunk". The success rate of drugs that have reached phase III is only slightly north of 50%.

Second, there is no way you could possibly figure out all the effects a particular drug has on the human body. You'd be doing research for the next 100 years and you still wouldn't come close. So what we do is we come up with a hypothesis (high HDL is good), we gather evidence in the most efficient manner we can (other drugs that raise HDL help prolong life in humans and animals), then we move forward with our BEST GUESS. That's how science works, you create a hypothesis, then test it.

Are our hypotheses wrong sometimes? Of course. Do we learn something from the failures? Yes. Trying a being successful 10% of the time is far better than not trying at all and being successful 0% of the time.

Merck's CETP inhibitor is in phase III right now and there is a chance that it will fail too. And I don't think any scientists feels that high HDL is the cause of reduced cardiac risks. A more accurate description would be to say "High HDL is associated with reduced cardiac risks, this drug increases HDL levels, so it stands a chance of reducing cardiac risks".

I think the author does a bad job of describing how scientists approach their work. If anything a scientist would be the first to call out a claim that something _causes_ something else. That's how their trained!

The articles criticism I think stems from the same feeling of discomfort I got when I understood a bit better how drugs are developed.

As a culture I think we have a certain faith in the medical system to save us from death, the same way previous generations looked to priests to save the spirit.

The inference you mention 'high HDL is associated with low cardiac arrest, therefore a drug that increases HDL might help is more vague than a layman expects. It's like saying 'I want a safe car, and German tend to be safe, therefore I will buy a German' - it's valid in the absence of a real understanding of how to specify and select a safe car, but it's more vague than you'd be comfortable with. You expect an engineering company to be able to specify a safe car based on deep knowledge. But because our understanding of the disease, and of what different chemicals can do is incomplete, a drug company can't do that. Instead, they follow as many hints as they can to select a chemical that might work, and then advance it through a series of progressively more expensive trials until they are pretty sure it does more good than harm.

That's a valid way of doing things, and at the moment it's all we can do. But it's not what a layman imagines, or certainly not what this one imagined. It undermines our sense of control - our sense that we are immortal and can get on with making an angry birds clone to get rich because there will be plenty of time to do the projects we want to after the payoff - it's not like we are going to die of heart disease, science has our back on that one!

Or maybe I'm generalizing my personal feelings too much?

No, you're onto something here. Modern medicine is not all powerful. It does some things very well, and we live much longer because of it, but there is still so much we do not understand. I'm thankful that there are those that put the time and money into this research that furthers our comprehension.

However, there are plenty of conditions you can develop where modern medicine is only able to contain the symptoms, rather than fix the problem causing them. Autoimmune conditions (such as MS) come to mind here.

I think that's the problem he's pointing out though with medicine: that we're unable to account for all the side-effects, that our hypotheses are often wrong (in drug development, its practically like a lottery if you start at pre-clinical), and that these gambles on drug development are getting way to costly for the healthcare system.

I think there needs to be revision of the experimental method overall, as the models of drug development in the 20th century simply aren't sustainable or efficient for the diseases of the 21st century.

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