Why are pharmaceutical companies struggling to discover new drugs?
Current drugs affect “feedback loops” and pathways in the body. For example, diabetes drugs "target" the PPARy receptor, which decreases insulin resistence, decreases leptin levels, which increases appetite…
Current drugs also target the body’s signaling infrastructure (like hormones and neurotransmitters), as well as the channels that allow molecules like glucose to flow across cell membranes. In some cases, cancer and viral diseases (like HIV) can be modulated and controlled, since they are rapidly dividing and have a short lifecycle that can be interrupted with drugs.
In other words, drugs can affect the body to the degree that the body was designed to be affected, by leaving exposed "targets" to be exploited. Every hormone must have its receptor, as every general must have his troops, ready for action when the signal is given. That signal-to-receptor communication can be affected by drugs. Unfortunately, many of these easy targets and control points have already been exploited by existing drugs.
It's true that there are 5,000 proteins in the extracellular space, and these could potentially become new therapeutic targets in the future. Current drugs only target around 200-300 known targets, so this seems like a large opportunity.
However, it’s difficult to deliver drugs to those targets. Since drugs are usually taken orally and must survive the arduous journey through stomach acid and absorption through the gut into the bloodstream, they are limited to being small molecules. And because the blood circulates through the liver and kidneys and the rest of the body, current drugs often have toxicity issues and side-effects. Sometimes, a drug's target – often a specific protein – serves multiple purposes throughout the body, so affecting one target will affect them all. Obviously, finding alternative drug delivery strategies will be important.
Also, finding alternative therapeutics like proteins, antibodies and vaccines (instead of using small molecules) will become increasingly important. The hope is that these therapeutics can be tailor-made to affect specific targets in the body – in specific locations – and not cause all the side-effects.
Another issue has to do with human development. What can be affected by drugs after we're grown? Since the human body is mostly developed at an early age, it’s difficult to change our disease proclivities (or personality tendencies), since these are already manifest into our physical form. Can you give someone a personality overhaul with a drug (from depressive to optimist)? Not except in certain extreme cases. Since our brains are mostly developed at a young age, only small interventions are possible (from depressive personality to non-depressive, but not to optimist).
Another big issue is how human genetic variation affects our response to drugs.
So clearly the path forward is some sort of intervention prior to development – in other words, at the time of conception – otherwise it’s too difficult to change or modulate the trait or disease. This would involve a major education campaign for the public, to get them thinking about diseases – and enhancement – in a new ways.
