Source: The Wall Street Journal
Date: 1 October 2004

Memory drugs create new ethical minefield


Move over, botox. Although injections of the most potent natural toxin known to science are marketed as knife-free plastic surgery to reduce wrinkles, Botox treatment is actually a neurological intervention. The toxin blocks the release of a neurochemical, acetylcholine, from neurons. That makes it the opening act in what promises -- or threatens -- to be a significant new drama. Welcome to "cosmetic neurology."

Sure, there have been reports over the years of, shall we say, recreational use of prescription pharmaceuticals. Some musicians and nervous public speakers take beta blockers (a heart drug) to vanquish stage fright. Modafinil (aka Provigil) is a stimulant approved for narcolepsy, but it has an underground following among those who want to feel as alert and rested after five hours of sleep as after eight. Ritalin, for attention-deficit hyperactivity disorder, improves concentration and the ability to plan, making it popular among healthy adults who simply want an edge in multitasking.

A string of recent discoveries, many of them from small studies that have flown under the radar, suggest that this is only the beginning. Ritalin, for instance, specifically boosts spatial working memory, or the ability to remember layouts and locations. Just the thing for back-country hikers, perhaps, or architects mentally juggling blueprints?

Compounds called cholinesterase inhibitors boost levels of the neurotransmitter acetylcholine, which lets neurons communicate with each other. One, donepezil (sold as Aricept), is approved for Alzheimer's disease. But that may be only one of its talents. In a 2002 study, scientists gave donepezil to one group of healthy, middle-age pilots and dummy pills to another. The donepezil group did markedly better learning maneuvers in a Cessna 172 simulator, particularly those used in flight emergencies.

Some drugs that affect memory work very selectively. So-called CREB inhibitors (CREB is a protein essential for incising memories in the brain) "seem to selectively erase only disturbing memories," says neurologist Anjan Chatterjee of the University of Pennsylvania, Philadelphia. And propanolol, a beta blocker, enhances the memory of events that are emotionally charged and that the brain otherwise suppresses. It also seems to erase the negative emotions associated with bad memories. Healthy people given the drug recall disturbing stories as if they were no more emotionally charged than a grocery list.

It's not that neuroscientists are deliberately looking for drugs that might be used for cosmetic neurology. Rather, these more frivolous uses are being discovered serendipitously, often in research on serious neurological diseases such as stroke. For instance, scientists find that small doses of amphetamines help stroke patients undergoing physical therapy relearn motor skills, such as tying shoes and using utensils, better and more quickly than with therapy alone. Taken half an hour before a therapy session, amphetamines seem to promote what's called neuroplasticity, the ability of the brain to form new connections or strengthen existing ones between its neurons. Those connections underlie both simple and complex sequences of movement.

"With amphetamines, the effects of therapy are more pronounced," says Dr. Chatterjee. "And animal studies suggest that pairing amphetamines with motor training leads to greater brain plasticity."

The day may be coming when perfectly healthy people will pop speed before a tennis lesson or piano instruction, knowing it may stimulate the brain rewiring that underlies a perfect backhand or a flawless "Fur Elise." Botox, after all, originally received government approval to treat two serious eye-muscle disorders, and now aging boomers regard a quick fix as no more momentous than a swipe of mascara. Cosmetic neurology could well follow the same arc, which means that the time for neurologists to weigh in on the ethical implications of all this is now.

Those implications are profound. If drugs can improve learning, make painful memories fade and sharpen attention, should physicians prescribe them? Must physicians prescribe them? Must patients -- perhaps pilots compelled by an employer -- take them? Might one airline distinguish itself from competitors by advertising its donepezil-taking crews?

Dr. Chatterjee captures the dilemma in a paper he wrote for the current issue of Neurology: "The distinction between therapy and enhancement can be vague, particularly when the notion of 'disease' lacks clear boundaries. ... If one purpose of medicine is to improve the quality of life of individuals who happen to be sick, then should medical knowledge be applied to those who happen to be healthy," lifting patients from normal functioning to enhanced functioning?

We can wring our hands all we want about pills that make learning more effective without greater effort, offending the belief that gains should be hard-earned, or about drugs that selectively erase painful memories, evoking a Brave New World of the happily drugged -- and less-than-fully human. I have a feeling it won't make much difference. "Patient" has become synonymous with "consumer," someone unlikely to take kindly to physicians, let alone ethicists, blocking his or her pursuit of self-improvement and happiness.

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