[Paleopsych] Scientific American Mind: Smarter on Drugs

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Scientific American Mind: Smarter on Drugs
October 2005 Issue

We recoil at the idea of people taking drugs to enhance their
intelligence. But why?
By Michael S. Gazzaniga

Any child can tell you that some people are smarter than others. But
what is the difference between the brain of a Ph.D. student and the
brain of the average Joe? If we can figure that out, then a bigger
question follows: Is it ethical to turn average Joes into geniuses?
Evolutionary theory suggests that if we are smart enough to invent
technology that can increase our brain capacity, we should be able to
use that advantage. It is the next step in the survival of the
fittest. As noted psychologist Corneliu Giurgea stated in the 1970s,
"Man is not going to wait passively for millions of years before
evolution offers him a better brain."

That said, gnawing concerns persist when it comes to artificially
enhancing intelligence. Geneticists and neuroscientists have made
great strides in understanding which genes, brain structures and
neurochemicals might be altered artificially to increase intelligence.
The fear this prospect brings is that a nation of achievers will
discard hard work and turn to prescriptions to get ahead.

Enhancing intelligence is not science fiction. Many "smart" drugs are
in clinical trials and could be on the market in less than five years.
Some medications currently available to patients with memory disorders
may also increase intelligence in the healthy population. Likewise,
few people would lament the use of such aids to ameliorate the
forgetfulness that aging brings. Drugs that counter these deficits
would be adopted gratefully by millions of people.

Drugs designed for psychotherapy can also be used to enhance certain
regular mental functions. Just as Ritalin can improve the academic
performance of hyperactive children, it can do the same for normal
children. It is commonly thought to boost SAT scores by more than 100
points, for both the hyperactive and the normal user. Many healthy
young people now use it that way for that purpose, and quite frankly,
there is no stopping this abuse.

In a way, with these new compounds, we are reliving the stories
associated with better-known illegal psychoactive drugs. Morphine is a
terrific help with pain produced by burns and other somatic ills; it
is also a mind-altering substance that in some areas of society causes
tremendous social and psychological problems. Do we stop developing
such painkillers just because they might be misused? Even when the
issue is simple memory enhancement, we profess great social concern.
Why do we resist changes in our cognitive skills through drugs?

The reason, it seems to me, is that we think cognitive enhancement is
cheating. If, somehow, someone gets ahead through hard work, that's
okay. But popping a pill and mastering information after having read
it only once seems unfair.

This position makes no sense. Among the normal population are men and
women with incredible memories, fast learners of language and music,
and those with enhanced capabilities of all kinds. Something in their
brains allows them to encode new information at lightning speed. We
accept the fact that they must have some chemical system that is
superior to ours or some neural circuitry that is more efficient. So
why should we be upset if the same thing can be achieved with a pill?
In some way, we were cheated by Mother Nature if we didn't get the
superior neural system, so for us to cheat her back through our own
inventiveness seems like a smart thing to do. In my opinion, it is
exactly what we should do.

Memory Enhancers

Already available, or making their way through the Federal Drug
Administration's approval process, are several cognitive enhancers
that reportedly improve memory. These are also being called smart
drugs, or nootropes, from the Greek noos, for "mind," and tropein, for
"toward." Whenever a study shows that a certain chemical produces even
a moderate increase in memory in an animal population (be it fruit
flies, mice or humans), one of two things happens. If the compound is
not on the market, a pharmaceutical company quickly jumps in to
exploit the finding. If the drug is already on the market but is used
to treat a known ailment--for instance, Alzheimer's or
attention-deficit hyperactivity disorder--a surge takes place in
off-label use, for a purpose other than the intended application. Some
regulated smart drugs are currently on the market, as are unregulated
herbal medications. Entire stores called smart bars have popped up
along the West Coast to sell these items.

Work on memory enhancers may be furthest along. Eric R. Kandel of
Columbia University, who won a Nobel Prize for his research on
learning and memory in the sea slug Aplysia, is one proponent. He
found that learning occurs at the synapse (the junction between two
neurons) by several means. The synapse is enhanced when a protein
called CREB is activated, and CREB plays a role in memory formation in
fruit flies and in mice. With these discoveries came the 1998 birth of
Memory Pharmaceuticals, Kandel's Montvale, N.J.-based company, which
hopes to formulate a drug that will raise the amount of CREB in the
human neural system and thus facilitate the formation of long-term
memories. One of the most promising chemicals is called MEM 1414. If
clinical trials go well, MEM 1414 could be on the market after 2008.
At least one other company, Helicon Therapeutics in Farmingdale, N.Y.,
is also investigating CREB to improve human memory formation.

Alternative drugs are also in the works based on other brain
mechanisms. Before a neuron naturally increases CREB, certain channels
on its membrane must open to allow positive ions to flow into the
cell. The ions then trigger a cascade of events leading to the
activation of CREB. One channel of interest is known as NMDA. In 1999
Joseph Z. Tsein, Ya-Ping Tang and their colleagues, then at Princeton
University, discovered that increasing the number of NMDA receptors in
the mouse hippocampus led to better performance on a spatial-memory
task. Now researchers and pharmaceutical companies are pursuing NMDA
receptor agonists (they combine with the receptors) as nootropes. At
least a dozen new drugs of this kind are making their way toward
clinical trials.

Scientists have known for years that more commonplace chemicals such
as adrenaline, glucose and caffeine increase memory and performance.
We all know it, too: procrastinators find clarity of mind in the
adrenaline rush to meet a deadline; we try not to work "on an empty
stomach"; and we are willing to pay a premium for a vente latte--all
testimony to our appreciation of these legal activities.

Self-medicating with Starbucks is one thing. But consider the
following. In July 2002 Jerome Yesavage and his colleagues at Stanford
University discovered that donepezil, a drug approved by the FDA to
slow the memory loss of Alzheimer's patients, improves the memory of
the normal population. The researchers trained pilots in a flight
simulator to perform specific maneuvers and to respond to emergencies
that developed during their mock flight, after giving half the pilots
donepezil and half a placebo. One month later they retested the pilots
and found that those who had taken the donepezil remembered their
training better, as shown by improved performance. The possibility
exists that donepezil could become a Ritalin for college students. I
believe nothing can stop this trend, either.

This anecdote reminds us that the unintended use and misuse of drugs
is a constant. Trying to manage it, control it and legislate it will
bring nothing but failure and duplicity. This fact of life needs to be
aired, and our culture needs to reach a consensus about it. Aricept
(the commercial name for donepezil) works, caffeine works, Ritalin
works. Individuals will use such drugs or not use them, depending on
their personal philosophy about enhancement. Some people like to alter
their mental states; others do not.

My guess is that, on average, adults will choose not to use memory
enhancers or the theoretically more obscure IQ or cognitive enhancers.
Why? Because when memory is in the normal range, we adapt to its level
and set our personal psychological life in that context. Increasing
our memory capacity might send a ripple effect across the landscape of
our daily lives. After all, we spend a good part of each evening
trying to forget many of the day's memories. Over a lifetime we have
built up our personal narrative based on the efficiency of our memory
and our capacity to forget. Any significant or even slight change in
these capacities will have to be integrated into the backbone of that
narrative, changing the mental life of a person.

For a society that spends significant time and money trying to be
liberated from past experiences and memories, the arrival of new
memory enhancers has a certain irony. Why do people drink, smoke
marijuana and engage in other activities that cause them to take leave
of their senses? Why are psychiatry offices full of patients with
unhappy memories they would like to lose? And why do victims of
horrendous emotional events such as trauma, abuse or stressful
relationships suffer from their vivid recollections? A pill that
enhances memory may lead to a whole new set of disorders. Maybe the
haunting memories of a bad experience will become ever present in
consciousness after taking an enhancing pill. This problem and dozens
of others may well be the outcome.

Of course, many steps precede success in drug development, and some
critics doubt we will see these newer memory enhancers in our
lifetime. Although studies on animal models find that certain drugs
improve memory or performance on specific tasks, it is not clear that
they would help humans. Many nootropes that were promising in lab
animals have failed miserably in human clinical trials. Is this
because millions of years of evolution have led to a human brain whose
neurochemical concentrations are at optimal levels? Another hurdle for
drugs is their potential to cause deleterious effects. Some accounts
of mice with altered "smart" brains, for instance, show that the mice
are not only more receptive to learning but are also more sensitive to


Enhancing memory is one issue. Making people smarter--more able to
contemplate complex ideas with greater ease and facility--somehow
seems more problematic. Do we want a nation full of Harvard graduates?
On the surface it seems insane. But the basic science suggests that
superintelligence is not far-fetched.

Defining what it means to be "smart" has frustrated psychologists for
years. IQ and SAT tests, though long-standing indicators of academic
success, are far from perfect indicators of success in the "real
world." Intelligence tests, especially the IQ test, measure people's
analytical skills, verbal comprehension, perceptual organization,
working memory and processing speed. This type of intelligence is
called psychometric intelligence, and although it is not the only type
(some researchers believe in "multiple intelligences," even including
athletic ability), it is testable and so remains one of our primary

In 1904 Charles Spearman, an English psychologist, reviewed the
literature of the 19th century on intelligence and found that people
who performed well on one test of intelligence seemed to perform well
on all others. Spearman theorized the existence of a "general
intelligence," which he termed g, that is used to process many domains
and thus makes some people good at nearly all intelligence challenges.
Many investigations since 1904 have supported Spearman's idea, and the
current consensus among scientists and psychologists is that a g
factor accounts for a great deal of the variance in intelligence test

Recently geneticists have discovered that even such abstract qualities
as personality and intelligence are coded for in our genetic
blueprint. Studies of the genetic basis of g are just beginning, and
because g most likely arises from the influence of many genes, the
hunt will be a long one. Yet one study has already found that a gene
on chromosome 6 is linked to intelligence.

So-called genetic brain mapping could help the search. Scientists are
looking at the structural features (size, volume, and so on) of the
brains of many individuals, including twins, familial relatives and
unrelated individuals. By scanning all these brains in magnetic
resonance imaging machines and looking at the differences, researchers
have been able to determine which areas of the brain are most under
the control of genes. These studies have emerged only in the past
three to four years. Geneticists hope that once they know which brain
areas are most affected by heredity, they can figure out which genes
are responsible for those regions. With this kind of reverse mapping,
the experts should be able to learn more about the genetics of

Geneticists and neuroscientists seem to be in agreement: the genes
that affect intelligence may be coding for the structure and functions
of specific brain areas that underlie Spearman's g. When researchers
combine brain mapping with IQ tests, they can begin to tease out the
correlations between the size, structure, and volume of brains and
intelligence. Neuroscientists have determined that overall brain size
has a statistically significant correlation with IQ. More detailed
investigations show that the amount of gray matter--consisting mainly
of the cell bodies of neurons--in the frontal lobes varies
significantly with differences in intelligence scores. That suggests
the frontal lobe may be the location of g.

Indeed, John Duncan and his colleagues at the Medical Research Council
in Cambridge, England, who put smart volunteers through a multitude of
mentally demanding tasks, found that the lateral part of the frontal
lobe on both the left and right sides may be the resting place of
general intelligence. While undergoing positron-emission tomography
(PET) scans, Duncan's subjects selectively activated the lateral
frontal cortex during several intelligence tests. Some researchers are
skeptical of the importance of Duncan's study, saying it is
"suggestive" at best because we do not yet fully understand what the
frontal lobes do. But his findings solidify the fact that we have
entered a new age in scientific history--an era that allows
neuroscientists to investigate individual differences in intelligence,
previously a field only for psychology.

Accordingly, a robust literature concerning neural differences in
intelligence has arisen. Further support for the frontal lobe's role
comes from the observation that people with frontal lobe damage
usually score 20 to 60 points lower on IQ tests than others. These
people also have deficits in what is called fluid intelligence, which
decreases with age and includes abstract reasoning, processing speed,
accurate responses during time constraints and use of novel materials.

Smarter or Just Faster?

The future is here. We have isolated one gene involved in
intelligence, and others will follow. We know which parts of the brain
are influenced by particular genes and which parts correlate with high
IQ. We also know some of the neurochemicals involved in learning and
memory. With such knowledge, we will gain understanding of what needs
to be manipulated to increase intelligence in people who were not
blessed with brilliance in their genomes or further increase the
intelligence of those who were. Gene therapy could insert, delete,
turn on or turn off genes that we find to be associated with

My own belief is that none of this threatens our sense of self. The
opportunities to enhance one's mental state abound. "Smart" describes
how well one processes information and figures out tasks. Once
something has been figured out, much work must then be applied to the
solution, and the smartest people in the world rarely say that the
task is easy. They have worked hard to achieve insight and solutions.
So we may all get faster at figuring out new problems, but it is not
clear what it would mean to get smarter. "Smarter" is frequently just
another word for "faster."

Whatever happens, we can be sure that cognitive enhancement drugs will
be developed and that they will be used and misused. But just as most
people do not choose to alter their mood with Prozac and just as we
all reorient our lives in the face of unending opportunities to change
our sense of normal, our society will absorb new memory drugs
according to each individual's underlying philosophy and sense of
self. Self-regulation will occur. The few people who desire altered
states will find the means, and those who do not want to alter their
sense of who they are will ignore the drug potions. The government
should stay out of it, letting our own ethical and moral sense guide
us through the new enhancement landscape.

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