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May 21, 2002

The Neuroethics of New Drugs and Technology
By Lisa M. Krieger, (c) Mercury News, May 21, 2002


It's another sleepless night at Stanford University.

But unlike the legions of students dozing over textbooks, volunteers at the Stanford Sleep Disorders Lab have pharmaceutical help: a controversial new drug called Provigil.

The medication, whose name is an abbreviation of the words "promotes vigilance,'' keeps the mind fully awake and attentive without the euphoric "buzz'' or jittery nerves of amphetamines and caffeine. It could prevent deadly mistakes by sleep-deprived truck drivers, doctors and other nighttime workers -- but also poses the risk of misuse in a culture fueled by a 24/7 ethos.

Provigil is but one of many provocative new tools to come out of the growing field of brain research. As scientists probe deeper into the brain's chemistry, they are learning more about what makes people feel alert, energetic, depressed, angry or serene.

The tools and technologies -- from drugs like Provigil to implantable brain chips, neuro-imaging techniques and brain-scan lie detectors -- offer new ways to alter and explore human cognition. But what's safe? What's ethical?

Those were the questions pondered last week at a first-ever conference sponsored by Stanford and the University of California-San Francisco. Scientists at the conference on "neuro-ethics'' debated the ethical and policy challenges posed by a growing knowledge in brain research.

"In the future, basic research in neuroscience may transform our understanding of human nature,'' said Barbara A. Koenig, executive director of the Stanford University Center for Biomedical Ethics. "Studying the brain offers a seductive promise: the ability to make assessments about people, their motivations, desires and characteristics.''

The conference, held in San Francisco, brought together ethicists, neuroscientists and those concerned with social policy to begin a dialogue that they hope will spread. Experts at the conference predicted that advances in brain science will influence a range of domains -- and change
many aspects of our lives.

Mapping Criminal Minds

Can we determine who is likely to commit a violent crime? Should those with brain injuries or other anomalies be considered culpable for their crimes?

A technique of ``brain mapping'' scans the brain of criminal suspects to see if they recognize incriminating images. It is under study at Brain Fingerprinting Laboratories of Fairfield, Iowa, where scientists interrogate suspects by checking their EEGs for P300 waves. These waves are
produced when the brain encounters words or images that it recognizes.

A new high-tech version of the lie detector -- an elaborate brain-imaging machine -- could usher in genuine thought police. Dr. Daniel Langleben of the University of Pennsylvania, a psychiatrist, has found that when people lie, brain scans reveal increased activity in several regions of the brain.

While the idea of monitoring brain waves isn't new, the technique has become more precise. Someday, say proponents, it will be possible to recognize brain waves emanated by guilty thoughts. They predict that the day will come when it will be possible to scan the skulls of everyone going through airports to search for potential hijackers.

Brain imaging could also contribute to the study of people in prison with a traumatic brain injury -- which may be a factor in some types of violent behavior.

"It may be possible in the future to determine whether a specific brain disease or injury impairs a person's ability to control impulses and behavior,'' said William J. Winslade, professor of law at the University of Texas Medical Branch. ``It's very relevant to the question: Can you control your conduct -- in other words, do you have legal responsibility?''

But the risk of error troubled many scientists at the San Francisco conference.

``It raises the question of whether such evidence should be used in legal settings,'' said Daniel L. Schacter, professor and chairman of the department of psychology at Harvard University.

Medication effects

``The impact of neuroscience -- through psychopharmaceuticals -- is already  apparent in educational settings,'' said Stanford's Koenig. High percentages of children, particularly boys, are prescribed medicines such as Ritalin for conditions that may not be clear-cut brain diseases, she said.

Equally controversial is the effort to speed up and deepen attention through pharmaceuticals such as Provigil. If Provigil works for all-night truck drivers, won't it also help students cramming for exams? Or a working parent who has been up all night with a sick child?

The volunteers in the Stanford trial arrive on campus during an evening when they're off work. They're given two capsules of Provigil or an inactive placebo, then are put to work on a battery of physical and mental tests.

``Most people report feeling naturally awake and refreshed. They don't feel like they're on anything; they're not feeling stimulated or euphoric. They're not jittery or anxious. They just feel awake,'' said Paul Stowers, a clinical research coordinator at the Stanford Sleep Disorders Clinic, who has seen the medication's effectiveness in combating symptoms of narcolepsy, a sleep disorder for which use of the drug is legally approved.

The drug works by increasing neuronal activity in the hypothalmic-arousal region of the brain, an area responsible for normal wakefulness.

As its reputation grows, doctors soon may find themselves faced with a difficult question: When is sleepiness a sickness? And should you prescribe medication for a student or worker who is intentionally sleep-deprived?

``There could be misuse, where someone does not have a medical condition but wants to stay awake,'' Stowers said. ``But we believe the actual abuse potential is quite low. People with a history of substance abuse don't like it because there's no `rush.' It doesn't really do anything.''

In the future, other medications may enhance the mind by boosting memory. Scientists predict that compounds developed to treat Alzheimer's will lead to substances that boost intelligence.

One such compound, NGD97-1, alters brain chemistry to increase the ability to form memories. NGD97-1 targets a brain neurotransmitter whose job it is to reduce the ability to form a memory. By blocking this chemical's effect, the drug boosts memory. It is being tested for its effectiveness in
reversing memory loss that afflicts those with degenerative brain conditions.

At the San Francisco conference, Erik Parens of the bioethical think tank the Hastings Center of Garrison, N.Y., warned that if the drugs were available only to wealthy students willing to pay to sharpen their minds, it could create an unfair advantage -- and, over time, increase the gap between the haves and have-nots.

"If there is a disease that causes an impairment in the ability to function, then memory-enhancing drugs are OK,'' said Schacter, of Harvard. ``The question becomes different when you look at trying to depart from the baseline level of function -- then, stickier questions arise.''

Arthur Caplan, professor of molecular and cellular engineering and chief of the division of bioethics at the University of Pennsylvania in Philadelphia, disputed the concerns.

"The notion of enhancement is deeply ingrained in our culture,'' Caplan said. "The only debate about the Kaplan SAT prep test is how many weeks to attend. What about spending $25,000 a year to send your kid to private school? Nobody says, 'You should be ashamed, you're giving your child an
advantage.' ''

Mechanical Manipulations

It's not just brain scans or pills that could change us, scientists said. Implanting fresh cells, or even computer chips, in an ailing brain could make the question "Who am I?'' an even more complex one.

Earlier this month, a group of scientists produced the ultimate lab rat -- an animal that can be guided by remote control over fences, up trees and across rubble. Researchers from the State University of New York and Drexel University implanted electrical probes in critical centers of the brain that affect what an animal senses and how it behaves. They then trained rats to respond to impulses sent through implants.

Once trained, the animals could be controlled by an operator with a laptop computer transmitting to a small receiver worn by each rat.

In related research using electrodes, a monkey at Brown University wore a fingernail-size brain implant allowing him to move a cursor on a computer screen just by thinking.

The drive behind such research is a humanitarian one -- finding better ways to help people disabled by injury or stroke communicate. It raises the hope that paralyzed people might one day be able to control complex devices with their minds.

"All these things create a shift in who we are and where we're going,'' said Paul Root Wolpe of the Center of Bioethics at the University of Pennsylvania. "Where is the beginning, or end, of the `tech' me and the `non-tech' me?''

Such tools may have dire ramifications in a world where science alters human nature, said Dr. William Hurburt, professor of biology at Stanford University.

"We're the products of 4 billion years of evolutionary history. Human beings are all-purpose organisms -- if you make us stronger one way, we may be weaker in another,'' Hurburt said.

While emerging tools of neuroscience may be benign, even life-saving, we must be cautious how we use them, said Parens of the Hastings Center. 

"I worry that our increased use of medical technologies will reduce the range of ways that it's acceptable to be,'' Parens said. "If more healthy adults use Prozac, for instance, what does it mean to our society that we're all more assertive, confident, resilient people?

"We need to remember that there are a lot of different ways to be in this world.''

If You're Interested

Volunteers interested in participating in a clinical trial of the drug Provigil can call the Stanford Sleep Disorders Clinic at (650) 498-7352.

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