Neuropharmacology and Scientific Progress

Over at Freakonomics, they invited several prominent thinkers to weigh in on a rather lofty question: How much progress have psychology and psychiatry really made?

The answers are mostly interesting, with nearly everyone agreeing that the sciences of the mind and brain have made tremendous progress. That is, of course, the correct answer. When you think that, one hundred years ago, Ramon y Cajal had just published his "speculative cavort" laying out the neuron doctrine, or that we still had no effective treatments for any mental disorders (the frontal lobotomy would become popular a few decades later), it's hard to deny that neuroscience, psychology and psychiatry have all made tremendous strides. It's a classic example of the upward slope of science.

And yet, that easy answer also elides some interesting conundrums. I'd like to focus on the disconnect between progress in basic research and advances in neuropharmacology. As I noted above, science has learned an astonishing amount about those trillion interconnected neurons inside the skull. We've reduced the mind into a byzantine list of kinase enzymes, synaptic proteins, microtubules, neurotransmitters, etc. Consciousness is nothing but a certain kind of chemistry.

At the same time, the medical sciences have come up with some rather effective drugs that have helped treat a wide range of mental illnesses, from depression to schizophrenia. At first glance, it might appear that these new drugs are the payoff of basic research, that we've learned how to treat the mind because we know so much about the brain. But I'm not sure that's right. Prozac, after all, was first invented as a treatment for high blood- pressure. (It worked in animals, but not humans.) And even though Prozac and other SSRI's are prescribed in dizzying numbers, we still don't know how they really work. (The over-simplified serotonin hypothesis has been largely discredited.) Or look at addiction, one of the most devastating mental illnesses. In recent decades, neuroscience has learned a tremendous amount about the substrate of addiction, with much of the work focusing on the dopamine reward pathway. And yet we're still giving people methadone, which was invented in 1937. Neuroscience knows a lot about the pathways of long-term memory, having identified plenty of pertinent kinase enzymes (CREB, PKC, etc.),and yet where are the memory enhancing drugs? Why are still taking gingko biloba, which doesn't even work?

I certainly don't want to diminish the notable successes of the 20th century, where neuroscience and medicine have made strides by working together. (Parkinson's comes to mind, where basic research into dopamine and the basal ganglia has led to dramatic improvements in patient care.) But I think that, while there has been real progress, the reality of progress has been a little messier than the narrative. I have no doubt that the billions of research dollars we've poured into neuroscience will have tangible and dramatic medical benefits in the future. I'm just not sure the future has arrived yet.


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All around neuropharmacology BigCheez Floyd Bloom has a presentation I've heard him give a time or two where he points out the fact that just about all of our mainline brain drugs- antipsychotics, antidepressants, anxiolytics - started with serendipitous observations. Or crude empiricism ("Hmm, let's see if this works") as opposed to so-called "rational drug design" or informed development. I gotta see if he ever wrote it up as a review or something like that..

I dunno, does agonist therapy count as a therapeutic drug? And I would be very surprised if this approach didn't pre-date methadone anyway, I'm thinking the quack/patent medicine era in which opium or laudanum addicts were treated with opiate-containing "remedies". hmmm, I need to look into that too.

Another good example of the "accidental" discovery of a psychoactive drug is iproniazid, the first anti-depressant. It's a derivative of isoniazid, the first anti-tuberculosis drug, and was tested for that purpose, when it was discovered that it made tuberculosis patients "inappropriately happy."

On the other hand, don't put down use of an older drug just because it's old. Methadone is used because it works better than anything else we've got. Now maybe some more research needs doing to find a better drug, but until then we use what we have. (And it's cheap because it's generic!)

Progress in neuroscience (and other areas - where is the cure for cancer) can be remarkably slow, and as a neuroscientist, somewhat discouraging. On the other hand, science often moves in jumps after long periods of piddling around (punctuated equilibrium?). Lets hope the current piddling period will come to a crescendo soon! Somethings got to be done about the absurd over-prescription of the current batch of pyschopharms.

Understanding the brain has come a long way but we have so much further to go.

When our family went to see the neurology clinic with our daughter we left with an inconclusive diagnosis. The Dr's parting shot was, "come back in five years, we'll know so much more."

A good friend died of brain cancer recently, he lived with it for years, his first surgery coming before the advent of the gamma knife. Who knows where he would be if the gamma knife had been there when he was first operated on.

My Grandmother's depression went untreated and was debilitating for her. Who knows what her life would have looked like had she lived in our time.

Knowledge evolves, building on history whether by accident or by careful study.

I'm a civil engineer by trade, we know a lot about our field because people have been building for millenniums. We learned about substrate and foundations from the folks who built the Cathedral Tower of Pisa in 1173 and yet a bridge in Minneapolis fatally failed just last year. We're still learning.

The brain is just a newer horizon. Keep up the good fight.