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http://www.sciam.com/print_version.cfm?articleID=31373133-E7F2-99DF-3B50B89EA1ADBBFB
ScientificAmerican.com
November 29, 2006
Juicing the Brain
Research to limit mental fatigue among soldiers
may foster controversial ways to enhance any person's brain
By Jonathan D. Moreno
Physicians have long tinkered with ways to
"improve" the human brain, but as our
understanding of that organ's inner workings
quickly grows, artifi-cial enhancement is
becoming more feasible. Military research is at
the forefront of this work, much of it focused on
drugs. The goal is to pro-duce a better soldier,
but the emerging techniques could just as easily be applied to any individual.
The military wants to juice up personnel's brains
because the human being is the weakest instrument
of warfare. Although for centuries astonishing
and terrifying advances have been made in the
technology of conflict, soldiers are basically
the same. They must eat, sleep, discern friend
from foe, heal when wounded, and so forth. The
first state (or nonstate) actor to build superior
fighters will make an enormous leap in the arms
race. In the short run, researchers are trying to
devise aids that would overcome a person's
inherent limitations, such as mental fatigue.
Long-term results could lead to individuals
everywhere who are tireless, less fearful or even better speakers.
Sleepless in Battle
Reducing human error caused by mental fatigue is
crucial because death by "friendly fire" is a
shockingly frequent occurrence. These tragic
mistakes can partly be attributed to the sleep
deprivation that accompanies lengthy deployments.
An investigation into a 2002 incident in which
two American pilots accidentally killed four
Canadian soldiers and injured eight others in
Afghanistan provided an unexpected glimpse into
the U.S. Air Force's interest in sleep. Unnoticed
by many, the pilots' attorneys in the resulting
court-martial cases pointed out that their
clients had been taking Dexedrine, sometimes
called the go pill, otherwise known as speed. It
was alleged that amphetamines such as Dexedrine
are commonly prescribed to keep pilots alert for
30-hour missions, even though questions have been
raised about safety. Use of such drugs can also lead to dependency.
The air force is considering alternatives to
amphetamines, in particular a medication that has
also gained the attention of long-distance
business travelers: modafinil. Marketed as
Provigil, it was approved by the Food and Drug
Administration in 1998 to treat narcolepsy and to
help control sleep disorders associated with
diseases such as Parkinson's, Alzheimer's and
multiple sclerosis. Modafinil is not a
traditional stimulant; rather than bombarding
various parts of the brain with arousal signals,
it apparently nudges the brain toward wakefulness
through specific pathways, perhaps by increasing
serotonin levels in the brain stem. The precise
mechanism is still not well understood.
The temptation for healthy people to use such a
drug is tremendous; some individuals report that
a dose leaves them as refreshed as a short nap.
Frequent fliers already get prescriptions for the
stuff, and it is sure to be the next craze on
college campuses among students who want to pull
all-nighters or just be able to party hearty for
days. Long-distance truck drivers are also
obvious candidates for use and, perhaps, abuse.
Neurostimulation might improve cognition during
confusing battles or offset sleep deprivation.
Workers who shift from day to night schedules and
back again are also interested. They often
complain of drowsiness during the work period
and insomnia when they want to sleep. The Air
Force Office of Scientific Research and Cephalon,
Inc., in Frazer, Pa., sponsored a study by
Harvard University and the University of
Pennsylvania in which 16 healthy subjects were
treated like shift workers: they were deprived of
sleep for 28 hours, then obliged to sleep from 11
A.M. to 7 P.M. for four days and to stay awake
those nights. The subjects on modafinil did far
better on cognitive tests than those on a sugar
pill. Double-blinded, placebo-controlled studies
have shown that some subjects can stay awake for more than 90 hours.
A few news outlets have made unconfirmed claims
that American soldiers were using modafinil on
the way to Baghdad in 2003. That would not be
surprising. Minimizing the need for sleep has
been a holy grail for war planners since time
immemorial. Guards at China's Great Wall chewed
an herb containing ephedrine; Incan fighters
munched on coca leaves; 19th-century Bavarian
officers gave their men cocaine; soldiers from
several countries used amphetamines during World
War II; and, of course, armies consume countless
tons of caffeine and nicotine. French soldiers
took modafinil in the first Gulf War, and the
Guardian newspaper reported in 2004 that the
U.K.'s Ministry of Defense had purchased 24,000 tablets of the drug.
Preventing Mistakes
Despite the interest in modafinil, questions
persist. Does it mask natural sleep needs but
fall short in keeping people as functional as
they think they are? This could be critical for
pilots and soldiers, who should not overestimate
their readiness. After prolonged use, the
endocrine and immune systems may be compromised by lack of sleep, too.
Military scientists are examining the safety
issues. One researcher at the air force's Brooks
City-Base in San Antonio told Pentagram, an
online newsletter, that "all indications say
modafinil is a safer drug, but we don't know that
for sure." But even if the compound proves safe
in terms of sound judgment in combat, what about
the effects down the road for people who have
been on and off the drug for years? The long-term
risks associated with sleep deprivation are not
well understood either. Evidence indicates that
during sleep, memory and learning are
consolidated and that the brain refreshes its store of energy.
Studies have shown that people who sleep only
four hours a day for an extended period have an
increase in insulin resistance, a prediabetic
symptom. But without a proven explanation for the
purpose of sleep, it is hard to assess the
downside of doing without, other than the obvious
discomfort that nonsleepers experience--the
attendant loss of concentration and the increased accident risks.
An intervention that minimizes the need for sleep
yet maintains cognitive capacity would be a
significant advantage for a military force.
Infantrymen commonly subsist on three or four
hours of sleep nightly for weeks. Special Forces
personnel may be awake for several days during
search and rescue operations. The Defense
Advanced Projects Research Agency (DARPA) is
spending $100 million in grants on "prevention of
degradation of cognitive performance due to sleep
deprivation." DARPA's Defense Sciences Office has
stated that "if you can prevent bad decisions
from being made during sleep deprivation, you can
dominate the battlefield." It is also interested
in how to reverse losses that might occur during
sleep deprivation and whether researchers can
"expand the available memory space, so that
people can retain cognitive function under
tremendous stress and sleep deprivation."
The military effort includes investigation of
another class of drugs, the ampakines, which show
some promise in treating dementia and symptoms of
schizophrenia by improving cognition when used
with antipsychotic medication. Clinical trials
have not found therapeutic value, but results
from a company-sponsored study at Wake Forest
University using an ampakine drug in
sleep-deprived rhesus monkeys were encouraging.
The monkeys' performance was reduced 15 to 25
percent when sleep-deprived, and reaction times
doubled. But a single dose of Ampakine CX717
eliminated their performance deficit and sleep
deprivation changes. An unpublished human trial
sponsored by the company that makes CX717
reported that 16 men deprived of a night's sleep
did better on memory and attention tests after
taking the drug. The scientist who conducted the
study said, "We didn't see any adverse events."
How Far Can We Go?
Military work is only the beginning of intense
efforts to control sleep-wake cycles. There is a
multibillion-dollar demand from civilians who
wish to sleep only when they want to sleep. The
neuroscientific key lies in a part of the
hypothalamus called the suprachiasmatic nucleus
(SCN), the brain's biological clock. About the
size of a pinhead and nestled deep within the
brain, the SCN, composed of 20,000 neurons, acts
as the pacemaker for circadian rhythms in
mammals. If the SCN is cut or removed in animals,
their sleep-wake cycle can be profoundly
disturbed. And when people are deprived of light,
the SCN runs on a 25-hour clock; for some reason
that is our innate length of a single day, which
helps to explain insomnia and other sleep
disorders in those who are blind. Though subject
to some variation, the clock can be reset by
exposure to light signals transmitted from the
retina, which is why we can function on a regular 24-hour cycle.
There are very few hard data showing that
prolonged sleep deprivation has truly deleterious
effects in humans, according to Harvard
neurobiologist Jerome Groopman. Yet University of
Pennsylvania researcher David Dinges has raised
provocative questions about Boeing Company's
plans for a jetliner that would fly around the
earth and need to land only once in 20 hours: How
should the crew sleep, if at all? What are the
rules that apply to sustained work on flights
like that? As Dinges says: "Now is the time to
have an open and frank discussion on how far we
will go as a culture. What are our priorities?
How regularly do we want to manipulate our brain
chemistry? What are the limits?"
Some insights may come from the animal world.
Dolphins seem to keep parts of their brains awake
to control their breathing and guide them to the
surface for air while the rest of their brain is
allowed to sleep. Otherwise they would drown.
Positron-emission tomographic (PET) scans are
beginning to reveal how their brain architecture
accomplishes this feat. If the mechanism can
somehow be simulated safely in human brains, it
will be hard to keep the method out of the hands
of civilians eager to get an edge in a competitive world.
Electricity and Magnetism
Another approach to enhancing cognitive abilities
may be electrical stimulation of select brain
centers. Physicians at the Rehabilitation
Institute of Chicago found that when they
implanted electrodes in the motor cortex of
stroke victims, patients regained about 30
percent of lost function as compared with 10
percent for other patients. Although the approach
is not perfect, the gains for those whose arms
had for years hung limply at their sides were
wonderful. Some stroke patients with speech
difficulties experienced improvement, too.
Unfortunately, the doctors do not know exactly why the added electricity works.
Eliminating fear genes could satisfy parents who
don't want to give birth to a "sissy."
An intriguing question is whether electrical
stimulation might help uninjured people exceed
their normal intellectual capacities. One
technique being explored is direct-current (DC)
polarization. At a 2004 Society for Neuroscience
meeting, researchers from the National Institutes
of Health reported that a tiny amount of
electricity delivered to the brain through an
electrode on the scalp produced measurable
improvement in verbal skills. They asked
volunteers to name as many words as possible that
began with a certain letter. The subjects showed
about a 20 percent improvement when the current
(two thousandths of an ampere, far less than that
needed to run a digital watch) was on.
Because the current ran through the prefrontal
cortex, the researchers speculated that the
firing rate of neurons was increased, activating
cells involved in word generation. The tiny
charge seemed to have no deleterious effects,
other than to leave certain individuals with an
itchy scalp. Moreover, the fact that the
technique does not involve surgery makes it more
practical than implanted electrodes.
Another noninvasive technique is transcranial
magnetic stimulation (TMS). A magnetic coil is
placed above the head, and magnetic pulses pass
through the cortex. Different kinds of pulses can
alter the firing rate of different sets of
neurons. Volunteers complain only about a
sensation of tapping on the skull as scalp
muscles contract and about a popping sound from the magnetic coil.
The therapeutic goal for DC polarization and TMS
is to treat patients with stroke or dementia. TMS
seems to target specific brain regions more
effectively, but DC polarization appears to carry
less risk of inducing seizures. Of course, the
long-term effects of frequent exposure to
electrical or magnetic stimulation are unknown.
Nevertheless, DARPA has awarded research grants
to explore whether neurostimulation can improve
impaired cognitive performance in confusing
battle circumstances or to offset sleep
deprivation, perhaps through helmets that deliver the tiny impulses needed.
Like so many potentially brain-enhancing
technologies, neurostimulation can easily be
oversold. Given how much we value cognition,
however, even a modest improvement would be
considered important by many people. Long-term
problems for military personnel might be hard to
identify and could seem worth the risk for even a
marginal gain in mental agility in life-or-death
situations. As neuroscientist Mark E. Huang of
the Rehabilitation Institute of Chicago told the
press in 2004: "There are many possibilities that
have to be answered ethically. If you want to
learn a new language, potentially the stimulator
might help. Would I recommend you do it for that
purpose? No. But down the road, who knows?
Obviously the sky's the limit, and we're still in the infancy stage."
No Fear
Possibilities for mind enhancement indeed abound.
A distinguished team of U.S. researchers reported
in 2005 that a gene called stathmin, which is
expressed in the amygdala (the seat of emotion),
is associated with both innate and learned fear.
The researchers bred mice without the gene and
put them in aversive situations, such as giving
them a mild shock at a certain point in their
cage. Normal mice exhibited traditional fear
behavior by freezing in place, but the altered
mice froze less often. And when both types of
mice were put in an open field environment--an
innately threatening situation--the mice without
stathmin spent more time in the center of the
field and explored more than the control mice.
Do individuals who have lesser stathmin
expression exhibit less fear? It is unlikely that
there is a one-to-one correspondence, because
humans are far more psychologically complex than
mice, capable of modifying their genetically
programmed behavior. Yet it is not difficult to
imagine that a military official who
overestimates the significance of genetic
information will someday propose screening
Special Forces candidates, or even raw recruits,
for the "fear gene." Indeed, a few years ago the
Burlington Northern Santa Fe Railway Company had
to pay $2.2 million to employees who had been
secretly tested for a gene associated with carpal
tunnel syndrome, even though the scientists who
developed the testing technique said it could not
work for that purpose. The company was trying to
see if the workers' medical claims were
attributable to their jobs or their genes.
If DNA testing for a fear gene is both
scientifically and ethically dicey, what about
setting out to create people who lack that
characteristic? Would breeding humans without
stathmin or other genes associated with fear
reactions engender more courageous fighters?
Would parents sign on for such meddling if they
harbored ambitions for a child capable of a
glorious military career or just didn't want to
give birth to a "sissy"? One problem, however, is
that fear or its functional equivalent is one of
those ancient properties exhibited by just about
every animal. It surely has tremendous survival
value. Removing it would be deeply
counterevolutionary and would almost certainly
generate numerous unintended and undesirable
consequences for the individual, let alone thrust
humans headlong into a fierce debate about
whether enhancing ourselves has gone too far.
Proponents of such artificial enhancements argue
that the changes may not be artificial at all. Is
there even a valid distinction, they ask, between
artificial and "natural" enhancements such as
exercise and discipline? Aren't we just trying to
gain whatever advantages we can, as we have
always tried to do, or are these techniques
cheating nature? Can we manage the consequences,
or are the risks for the individual and for humanity too great?
Is there even a distinction between artificial
aids like drugs and "natural" ones like exercise?
These questions are part of an ongoing argument
about whether we should use new discoveries in
neuroscience and other fields such as genetics to
improve ourselves, our descendants and perhaps
even the species. If it becomes acceptable to
enhance civilians, then it would be hard to
explain why national security agencies should be
barred from giving war fighters an edge. And if
it is not acceptable to enhance civilians, a
special case might still be made for tuning up military personnel.
National research on enhancement technologies
will require the close involvement of advisory
bodies with members both in government and
outside it, with as much transparency as
possible. Whereas some general principles should
be articulated and become part of our regulatory
framework, much of the hard work will have to be done on a case-by-case basis.
As Dinges notes, the debates are ones we haven't
had. Libertarians would argue that government
regulation would be overreaching, conservatives
would worry about changing human nature, and
liberals would worry about inequitable access to
whatever advantages neuropharmacology might
confer on those who are already relatively well
off. All these views deserve to be aired, and the
discussion needs to be moved onto our national policy agenda.
--
((Udhay Shankar N)) ((udhay @ pobox.com)) ((www.digeratus.com))
