A humorous analogy of where drug target therapies get it wrong (that sadly isn’t all that funny)

Often the pharmaceutical target is not – in itself the problem. I find the following analogy a useful way to illustrate this point: Imagine you work in a government and you notice that in your country there are too many ambulances circulating on the road.

“What can you do if there are too many ambulances on the road?”

As a person who has studied and is qualified for the job you do, you are well aware that too many ambulances is not a good sign. It is statistically correlated with a high death rate in society and a shorter expected life span of the average citizen.

Ambulances are easy to identify and count. They make a lot of noise.

Hence, you declare them a suitable target and dedicate a research budget to developing a method to reduce the number of ambulances.

One of your directors at a national research institute comes up with a genius solution: Fire the workers at the ambulance production factory. This has the unwanted consequence of increasing unemployment. It is known that this side effect is troublesome but still accepted since the benefits are considered more important.

However in order to address this inconvenient side effect - yet another round of funding to research, and there emerges an even better solution that reduces the impact on unemployment: reduce the supply of wheels to the factory. That way the workers stay employed, they just produce defective ambulances which don’t circulate on the roads. They accumulate in a parking lot and later get dismantled. Hense you save employement.

Again it is a benefits verses risk calculation: The benefits in terms of decreased noise pollution are invaluable, and the hospital emergency department is no longer overcrowded, cutting the hospital budget and saving health care workers from stress and professional burn-out.

Faulty logic? Yeah.

But this is really how it works with pharmaceutical targets. They focus on short term symptom repressive- half ass “solutions”. And since the human body is so innately resilient, they often get away with it – for a while at least.

You see – metaphorically speaking – if we return to the above analogy – what happens is the body is that the “civilians” prevent the population from declining as a result of the increased number of deaths (due to lack of ambulances) by giving birth to more children. There is much redundancy to life systems so problems can be compensated - albeit sub-optimally – a crucial aspect of survival of the species.

In biology, living systems always seek a return to HOMEOSTASIS of some sorts - even if a

modified or suboptimal one.

If you don’t bother digging too deep and just measure the population, you see the number of people living in your country has stayed the same. Sure tons of people are dying (what the hell) but they are being substituted by new births. (you choose to conveniently ignore the declining life expectancy data).

Apologies because I realize that logic is really getting twisted now and deeply disturbing.

In all this no one really bothered to ask the really “dumb” – innocent – question:

The same way way the child who yells out from the crowd:

“the emperor is naked!”

in the old story “the emperor’s new clothes”.

So what is this blatently obvious question?

“WHY are there so many ambulances on the road in the first place?”

I hope it is becoming clear that for research to really bring a breakthrough, it all comes down to starting out by learning some of the background & framing the right question.

You see now it start to get complicated and messy. There is no quick flashy budget change or policy intervention that will fix the real problem. In order to do that you need to examine things such as car accidents, domestic violence, sickness, alcohol abuse, safety standards on the work place, emotional health.. just to name a few.

“As often is the case, it all comes down to starting out the research by framing the right question.”

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