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3
Human Performance Modification as a Biological Problem
Several technologies that can affect human biological systems are fertile ground for
exploration of how human performance can be modified. These include tissue engineering,
methods for combating fatigue related to the operational cycles of the human body, and issues
associated with nutrition. Because nutrition was explicitly excluded from its task, the committee
has restricted its discussion to human tissue engineering and fatigue research.
TISSUE ENGINEERING
The modification of the cellular aspects of humans is a subject of active inquiry throughout
the world. The types of tissues that are being researched range from muscles (e.g., to increase
strength) to organs (e.g., to create replacement organs). The research is being conducted in sports-
medicine laboratories, genetic-engineering laboratories, and rehabilitative-surgery centers. The
committee found tissue engineering to be one of the most difficult subjects to review because it is
so vast, so varied, and so complex. Further, because the topic involves direct interference in the
human body, there are widely differing views around the world as to what kinds of research are
considered morally acceptable.
Tissue engineering can be defined as the use of cells, engineering, materials, and suitable
biochemical and physiochemical factors to improve or replace biological functions. Success has
been achieved in tissues that are thin membranes, that are avascular, or that have high
regeneration potential. For example, tissue-engineered skin, cartilage, bone, and corneas have
been used clinically (Khademhosseini et al., 2009).
There have been three approaches to tissue engineering: the conductive approach, using a
material to provide the structural framework for cell infiltration; the inductive approach, using
soluble materials to promote cell infiltration; and the cell-replacement approach, providing either
an allograft (from a donor) or an autologous graft (from the patient) to repair a tissue. Those
approaches have been successfully used clinically to improve regeneration. Tissue engineering
can be used to speed recovery and to improve the quality of the generated tissue.
In the case of cell-replacement therapies, the cell source is of great importance. With a
shortage of donor organs and available cells, stem cells are the primary alternative to isolating
cells from a patient’s tissue (Doss et al., 2004). Human embryonic stem cells, which have the
capacity to differentiate into all cell types, have resulted in the formation of teratomas1 when
implanted in vivo (Thomson et al., 1998; Caspi et al., 2007). Adult stem cells, which can
1
A teratoma is a “multi-layered benign tumor that grows from pluripotent cells injected into mice with a
dysfunctional immune system. Scientists test whether they have established a human embryonic stem cell (hESC) line
by injecting putative stem cells into such mice and verifying that the resulting teratomas contain cells derived from all
three embryonic germ layers.” National Institutes of Health, U.S. Department of Health and Human Services. 2011.
Stem Cell Information. Available at http://stemcells.nih.gov/info/glossary. Accessed August 10, 2012.
23
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24 HUMAN PERFORMANCE MODIFICATION: REVIEW OF WORLDWIDE RESEARCH
differentiate into several but not all cell types, have been in use for decades. Hematopoietic2 and
mesenchymal3 stem cells are commonly used but have limited capacity. Primary cells, or
terminally differentiated cells, lack the capacity to regenerate numerous times, and often cell
quality decreases with each passage.
Today, most tissues are too complex to be replicated. First, the ability to create a
vascularized tissue remains a fundamental challenge in the field. Mass-transport limitations
governing nutrients and waste affect the function and viability of a tissue (Allen et al., 2001;
Sachlos and Auguste, 2008). Microfluidic, capillary-like systems exhibit high resistance and
require substantial pressures to produce continuous flow. Second, the ability to organize cells in
three dimensions is limited. Hydrogel-based and scaffold-based matrices offer little help in the
assembly of cellular networks, which are important for cell–cell communication. For example,
the heart and muscles must contract synchronously. Discontinuities within the cell organization
can result in loss of function or abnormal gene expression, which can lead to a diseased state.
Thus, cell organization, mechanics, and electric signals must all be linked to produce a viable,
functional tissue.
Focused efforts have tried to repair tissue by mimicking 3-D tissue architecture, extracellular
matrix, and cell organization. For example, organ printing was established as a bottom-up
approach that uses 100- to 500-μm aggregates of cells, known as tissue spheroids, as building
blocks to make 3-D tissue constructs (Ruei-Zeng and Hwan-You, 2008). Robotic bioprinting of
hydrogel droplets containing cells can be used to dispense or digitally spray tissue spheroids to
achieve multicellular structures (Wang et al., 2006). Cells then self-assemble within and between
spheroids to form larger, integrated structures. However, mass-transport limitations hinder the
advancement of this technology.
In summary, the ability to enhance tissue performance is limited by (1) the need to obtain
adequate and substantial numbers of viable cells, (2) mass-transport characteristics that dictate
cell viability, and (3) the need to recapitulate the tissue architecture and cell organization that are
required for tissue function. Tissue-engineering methods are focused on clinical repair, and
current methods are unable to surpass the functioning of healthy tissue.
Worldwide Research
Tissue engineering has commercial applications in ligament repair and replacement, and
epidermal constructs. The committee found that the countries with companies that provide
products in this field include Australia, France, Italy, Germany, the United States, the United
Kingdom, Switzerland, Japan, and Korea. Research on organ regeneration and bone replacement
is also under way.
FATIGUE: JUDGMENT AND DECISION MAKING
Good human–machine system design exploits human strengths (such as pattern recognition
and decision making) and protects against human weaknesses. “The human operator brings much
more performance variability to a system than one finds in [reliable] software and modern
hardware. . . . Once an operator has been trained and is current in system operation, the greatest
2
“Hematopoietic stem cells are immature cells that develop into all types of blood cells including white blood
cells, red blood cells and platelets.” National Institutes of Health, U.S. Department of Health and Human Services.
2011. Stem Cell Information. Available at http://stemcells.nih.gov/info/glossary. Accessed July 31, 212. For more
information on hematopoietic stem cells, see http://stemcells.nih.gov/info/basics/basics4.asp. Accessed July 31, 2012.
3
Mesenchymal stem cells are “rare cells mainly found in the bone marrow that can give rise to a large number
of tissue types such as bone, cartilage (the lining of joints), fat tissue and connective tissue (tissue that is in between
organs and structures in the body).” Texas Heart Institute. 2009. Available at http://texasheart.org/Research
/StemCellCenter/Glossary.cfm. Accessed July 31, 2012.
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HUMAN PERFORMANCE MODIFICATION AS A BIOLOGICAL PROBLEM 25
contributor to variability in that person’s performance is cognitive fatigue,” especially during
night work (Folkard and Tucker, 2003; Miller 2005, 2010).
The human body has complex operational requirements, one of which is adequate rest.
During rest periods, such as sleep, vital functions occur (Matthews et al., 2012). When the body is
deprived of rest, specifically sleep, those functions do not occur, and the ability of the person to
perform degrades predictably. The effect is noticeable in both cognitive and muscular
performance. Sleep deprivation also causes substantial physiologic changes, such as increases in
blood pressure (Conquest, 1991; Matthews et al., 2012; Chan et al., 1993).
The need for sleep is complicated by the reaction of the human body to light and dark. Sleep
during periods of light is not as effective in operational restoration of the human mechanism as
sleep during periods of darkness. Research has shown that job effectiveness, as measured in terms
of the speed and accuracy of trained workers, is highest between 7 a.m. and 7 p.m. and lowest
during the predawn hours (Fokard and Tucker, 2003; Office of Technology Assessment, 1991).
Physical fatigue in people is manifested in deteriorated dexterity, decreased eye–hand
coordination, tremors, discomfort, and loss of strength and endurance. It is often not only how
long a person works or how much rest and sleep he or she receives, but also the type of physical
and mental workload that the person is subjected to while awake that determines whether fatigue
is present (Chaffin et al., 2006).
System design can play an important part in improving or optimizing the performance of
human elements in the overall system (Costa, 2001). Conversely, human performance can be
degraded by taking advantage of perturbations to normal operational cycles (for example,
attacking before dawn) (Gunzelman et al., 2012).
Some research in the various aspects of human fatigue is focusing on how human
performance can be modified—improved or degraded—through fatigue-related elements of
system design and performance (Matthews et al., 2012). Research tends to be focused on working
situations in which altered sleep patterns are necessary, such as military movements or shift-work
environments (Hull, 1990; Office of Technology Assessment, 1991; West et al., 2007; Samaha et
al., 2007).
It is clear that fatigue-inducing situations degrade human performance. They can lead to
dangerous situations, such as when a transport worker’s decision-making ability is degraded
because of fatigue. Research has shown that fatigue has serious effects on the human brain
(Reeves et al., 2006, 2007). But research results are mixed as to how to optimize human sleep
needs in operational environments that demand 24-hour activity, such as in medical facilities,
prisons, manufacturing plants, and telecommunications facilities (Costa, 2001). The optimization
of length and staggering of shift assignments are being studied, but no clear picture of a “right”
answer has emerged. Each environment has a different type of worker and different operational
requirements, and this may explain why the research findings are mixed.
Some technologies can affect fatigue. For example, there has been a revolution in the science
and technology of light-induced human performance modification. The use of spectrum-tuned
light sources can wake people up or cause them to become drowsy. Examples are the recent
identification of the melanopsin-pigmented retinal ganglion cell system, which is exquisitely
sensitive to 460- to 480-nm blue light, and the use of blue-light filtering (in Canada) and blue-
light treatment (in Europe) to affect human performance in 24/7 operations. The energy in that
narrow window—6 percent of the total visual light spectrum—can duplicate the effects of the
energy of the total light spectrum. These developments can be expected to influence the design of
lighting systems, computer display screens, and eyewear. For example, Casper (at the University
of Toronto) has shown that filtering out 460- to 480-nm light dramatically improves vigilance and
performance in the circadian nadir (Rahman et al., 2011); it reverses the nocturnal dip in
performance and provides users an enormous advantage in nighttime and early-morning
operations.
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26 HUMAN PERFORMANCE MODIFICATION: REVIEW OF WORLDWIDE RESEARCH
The practical applications of such technologies are being explored in various situations, such
as military deployments and long-haul trucking (Paul et al., 2007). Paul and his Canadian
colleagues have successfully countered jet lag and shift lag by timing light treatments in
conjunction with timing ingestion of sustained-release melatonin. Light treatments are also being
used in the treatment of seasonal affective disorder. The physiologic mechanisms are still being
explored (Boivin and James, 2005; James et al., 2004). A combination of the technologies with
pharmacologic agents, such as caffeine or melatonin, and structured changes in sleep patterns can
assist people who must move between time zones (Piérard et al., 2001).
Most fatigue researchers point out that the solutions to worker fatigue include the
participation of workers’ organizations, managers, and supervisors. Fatigue is difficult for people
to manage successfully apart from their work environments. Enormous strides have been made in
the design, development, and implementation of fatigue-risk management systems (FRMSs).
Regulations and laws have been passed that require FRMSs, as discussed in the comprehensive
FRMS guidance statement published by the American College of Occupational and
Environmental Medicine (Lerman et al., 2012).
Interestingly, some people are naturally fatigue-resistant (Aeschbach et al., 2003; He et al.,
2009; King et al., 2009). There might be an identifiable genetic component of that attribute that
has not yet been discovered. If such a genetic component is identified, it might be a useful target
for experimentation to help workers or soldiers to become fatigue-resistant.
Knowledge about the nature of fatigue associated with many kinds of specific jobs may be
used to optimize operational plans. International working-time regulations may affect military or
contractor duty periods during training. The accident and incident risks associated with fatigue
may be documented and quantified, and the results may inform operational planning. In the next
5 years, 12-hour shifts may come to dominate 24/7 operations because of the flexibility they
provide workers to structure their off-duty time. Technologies for ambient light treatment in the
nighttime workplace have been deployed commercially and may be used to enhance nighttime
work performance. Readiness-for-duty testing technologies have been deployed minimally in the
commercial world (Axelsson et al., 1998; Bloodworth et al., 2001; Campolo et al., 1998; Dwyer
et al., 2007; Laundry and Lees, 1991; McGettrick and O’Neill, 2006; Richardson et al., 2007;
Smith et al., 1998; Tucker et al., 1998; Williamson et al., 1994).
In the next 5-10 years, fatigue-risk modeling will become common in 24/7 operations.
Modafinil may be approved as an over-the-counter stimulant to be used somewhat like caffeine.
Top-down FRMSs will be common in 24/7 operations, and the practice of removing sleep debt
before critical operations will also be common. In the next 10-15 years, pretravel adjustment of
the circadian rhythm will become common, and on-duty napping during 24/7 and nighttime
operations will become an accepted practice. In the next 15-20 years, rapidly rotating and flexible
shift plans will be used in support of 24/7 operations, and more care will be taken to ensure that
enough personnel will be available to support four- and five-crew solutions to meet 24/7 work
demand (Axelsson et al., 1998; Bloodworth et al., 2001; Campolo et al., 1998; Dwyer et al., 2007;
Laundry and Lees, 1991; McGettrick and O’Neill, 2006; Richardson et al., 2007; Smith et al.,
1998; Tucker et al., 1998; Williamson et al., 1994).
There are some indications that physiological stimulation of the human body can interfere
with sleep biology (De Groen, 1979). At the crudest level, such stimulation might be a physical
nudge. At the most sophisticated level, it might be brain stimulation (Dimitrov and Ralev, 2009).
It is well within the realm of imagination to consider the potential of implants, such as electrodes,
that might provide such stimulation if a series of warning indicators were detected. Alerts based
on measurement of ocular movements and blinks have been used successfully to reduce
impairment caused by drowsiness in real time in equipment-operating tasks (Johns et al., 2007).4
4
Fletcher, Adam. 2012. “Technologies for Fatigue Detection and Management.” Presentation to the committee,
March 8.
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HUMAN PERFORMANCE MODIFICATION AS A BIOLOGICAL PROBLEM 27
The alerts have been effective temporarily, but additional research is needed to assess their full
impact on fatigue. Recent advances in integration of computing power into personally wearable
devices, such as smart wristwatches, will probably contribute to advances in the ability to
measure and respond to physiologic changes that indicate fatigue.
Worldwide Research
The committee found that open research in human fatigue is being conducted in several
countries: Belgium, Australia, the Netherlands, Germany, Canada, Japan, the United Kingdom,
the United States, Kuwait, Italy, France, Poland, and Singapore.
