ARTICLE IN PRESS

Technology in Society 29 (2007) 43–61

www.elsevier.com/locate/techsoc

Nanotechnologies: What we do not know

Vuk Uskoković
Jožef Stefan Institute, Advanced Materials Department, Jamova 39, 1000 Ljubljana, Slovenia

Abstract

This paper considers the impossibilities, uncertainties and undefined relationships that may be
involved in extending scientific and humanistic interest towards the development of nanosciences and
nanotechnologies. The author proposes a closed loop that moves from material properties, to
synthesis procedures, to applied functioning of nanoproducts and their place within ecosystems and
societies, to the design of novel features of nanomaterials. Unpredictabilities that may occur in the
transition from micro to nano within material structures are described. The paper then discusses
trial-and-error approaches and self-organization effects within every nanodesign procedure, and
considers the impossibility of forming perfect nanoproducts. Uncertainties arising from environ-
mental effects, and the extensive future use of nanoproducts within bio/technological interfaces pave
way for the study of GM case and discussion of sustainability and zero-waste potential.
r 2006 Elsevier Ltd. All rights reserved.

Keywords: Nano; Nanoscience; Nanotechnology; Genetically modified foods; Sustainability; Zero waste; Trial-and-
error approach; Bioengineering; Ecology

1. Introduction

This article identifies and discusses many of the functions of science today that seek to
produce new materials and technologies often referred to in conjunction with the word
‘‘nano.’’ I believe that keeping abreast with horizons of human knowledge enables modern
science to identify further discoveries as well as to develop advanced cultures and even
more complex bio-technological interfaces.
There are four sections in this paper. Section 2 discusses dramatic changes in material
properties that occur with the reduction of grain sizes to nanoscale proportions. Section 3

Tel.: +38614773900; fax: +38612561222.

E-mail address: vuk.uskokovic@ijs.si.

0160-791X/$ - see front matter r 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.techsoc.2006.10.005
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44 V. Uskoković / Technology in Society 29 (2007) 43–61

considers trial-and-error approaches that can be used to design novel nanostructures,

as well as the problem of constructing nanosized products by imposing ‘‘blueprints’’
on self-organizing natural patterns. The unpredictable ecological effects upon environ-
mental introduction of nanomaterials and nanotechnologies are discussed in Section 4, and
the paper concludes with consideration of the potential consequences of predefining
scientific research at the cost of further developments at fundamental levels of scientific
knowledge.
In order to interrelate the physical and chemical fields of nanomaterials science with the
mainly engineering-oriented field of nanotechnology, relations between preparation
processes, structural properties, and functions need to be understood [1]. The goal of
today’s nanomaterial scientists is controlling morphology (nanoclusters, nanowires,
nanotubes, etc.), structure, composition, and size—the features that define the physical
properties of the resulting materials [2]. As a paradigm within materials science and
engineering, the linear dependence between inherent properties of materials, procedures of
synthesis, and potential functions within techno-appliances is depicted [3].
The growing interest in nanostructured materials is the natural consequence of advances
and refinements of knowledge about the creative manipulation of materials. And the more
precisely nanomaterial properties are magnified, the more unusual and unexpected features
emerge. Unique research fields devoted to endeavours characterized by the prefix ‘‘nano-
’’—from physical modelling, to chemistry, to discourses on the ethical and eco-prospects of
industrial applications—have gradually developed. However, while the scientists’ ability to
make artificial changes in the features of nature has increased over time, enabling them to
routinely produce extraordinarily complex nanostructures, it should be remembered that
nanoparticles have been present since the beginning of planetary life and the earliest
appearance of mankind’s ability to produce arts, tools, and machinery [4,5]. Today’s keen
interest in anything nano in the scientific and popular media has undoubtedly been spurred
by large investment funds with a vested interest in the creation of ever-finer technological
products.
The term ‘‘nanotechnology’’ was first introduced by a Japanese engineer, Norio
Taniguchi. The term originally implied [6] a new technology that went beyond controlling
materials and engineering on the micrometer scale, which had dominated the twentieth
century. However, today’s meaning of the word relates more closely to the visionary
formulation of Eric Drexler [7], and corresponds to the atom-by-atom manipulative, hard-
tech processing methodology. However, due to many misconceptions, the latter approach
to nanodesign is today generally referred to as ‘‘molecular assembly.’’

2. When macro and micro become nano

Nanoscience is here defined as the study of phenomena and the manipulation of

physical systems that produce significant information (i.e., ‘‘readable’’ differences [8]) on a
spatial scale known as ‘‘nano’’ (109 m ¼ 1 nm), with critical boundaries that do not
exceed 100 nm in length at least in one direction. Therefore, nanotechnologies focus on
the design, characterization, production, and application of nanoscale systems and
components.
The boundaries between the physical regions of macroscopic, microscopic, and
nanoscopic are not sharp and they depend on the effects being considered [9]. However,
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reducing the grain size of a material below certain limit results in the appearance of either
new or changed properties of the material due to:

 inherent crystalline grains approaching the size of the characteristic physical lengths of
the relevant properties;
 an increase in the proportion of interface defects and their impact on dependent
properties; and
 the appearance of new structural properties that characterize the grain boundaries of
the material [10].

For example, a material comprised of spherical crystalline grains 3 nm in diameter finds

approximately half of its atoms positioned at grain surfaces, which implies more
pronounced reactivity of the system. However, a decrease in grain size, equivalent to an
increase in specific surface area of the system, indicates not only increased reactivity but
also that physical properties are no longer dominated by the physics of the bulk matter.
Since specific disciplines within materials science are normally divided based on the
properties of bulk materials, an understanding of the transition from macro to nano offers
the opportunity to bridge imposed gaps and create a new multi-disciplinary field of
nanoscience [1,9].
Physical properties such as electrical conductivity, microhardness, coercivity, and
permitivity decrease in proportion to the average particle size of a material. In case of
coercivity versus grain size dependence, however, two effects overlap: one valid for bulk
materials and the other appearing when grain sizes approach the sizes of magnetic
domains. In the former case, coercivity is inversely proportional to the grain size; in the
latter case, the H c ¼ f ðD6 Þ function coincides with experimental dependencies resulting in
the appearance of maximum at the point of coherence. Further, since mechanical failure of
a material frequently takes place through crack migration processes along grain interfaces,
the fact that materials with nanosized grains (down to 10 nm) are stronger compared
with their bulk counterparts implies significant modifications of strength and toughness
mechanisms as a result of the transition from bulk to nanoscale [11]. Metals that become
malleable when microstructurally arranged may prove to have unacceptable levels of creep
when their grains are reduced to nanolevel. In contrast, the formability of ceramics is
known to improve with the reduction of grain size towards nanoscale. As a result, simple
linear extrapolations down to nanolevel, using rules that are valid within micro domains,
do not work well in all circumstances.
By decreasing physical body sizes down to certain limits, the cohesive influences of
gravitational forces give place to Morse function-shaped electromagnetic forces and the
quantum effects that arise from electronic properties [9]. When the lower size limit of
nanomaterial grains approaches that of regular clusters, quantum effects overcome surface
effects and become the dominant factor in defining measured properties. Thus,
confinement effects modify electron energy levels, similar to a particle in a box, whereby
Coulomb blockade effect arises as a consequence of the discrete nature of electric charges.
Ultra-small capacitors at fine grain boundaries might be charged with even single
electrons, which strongly influence the subsequent transport of charges through the
material [11]. Giant and colossal magneto-resistance effects present additional behaviours
typical of systems comprising nanosized critical boundaries [12]. Owing to the complex
interplay between surface and quantum effects, each nanostructure can display an array of
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unique potential properties with even the slightest modifications, so specific discussions are
needed for each nanosystem.
It has been observed that insoluble substances become soluble, or that insulating
compounds become conductive when their constitutive particles are reduced to nanosize.
For example, gold is an inert and unreactive material in bulk atomic symmetries, but it
becomes a highly efficient catalyst as the transition to nanoscale is introduced; silver
nanoparticles exhibit bioactive properties that are not found in larger particles [13]. Soft,
malleable carbon in the form of graphite becomes stronger than steel, and aluminium can
spontaneously combust or even be used in rocket fuel following its transition to nanoscale
[14]. Although experiments have led to enormous amounts of data on the transitions from
micro to nano, there is still no theoretical scheme by which it would be possible to predict
how materials in general might behave when reduced to nanoranges.
The difficulty of communication between macroscopic and nanoscopic entities is the
central issue in the development of nanotechnologies. Increased sensitivity to environ-
mental effects, as dimensions are diminished towards nanoscale, represents a major
challenge. For instance, gaseous particles that are constantly being adsorbed and desorbed
from a device’s surface create weight fluctuations that might prove to be a significant
constraint in the development of everyday nanoappliances [15]. Also, ubiquitous, random
thermal fluctuations impose a ‘‘noise floor’’ below which it is impossible to discern signals
from background noise. Minimum operating power, normally 103–106 less than signal
levels used for optimal excitement of nanodevices, is therefore set as a fundamental
threshold for the operation of nanomolecular machines. According to the laws of quantum
mechanics, every form of measurement and communication necessarily perturbs the
measured and communicated system. Therefore, designing and performing feedback-
permeated macro-to-nano communications with quantum effects that become significant
in nano domain present additional challenges.

3. Approaches to nano design and technology

3.1. Bottom-up and top-down approaches

Nanotechnologies are generally considered to be technologies for the ‘‘bottom-up’’

creation of materials and devices, in contrast to traditional ‘‘top-down’’ industrial
technologies that cast, saw, and machine chunks of raw materials to produce precisely
formed products, small or large, ranging from integrated circuits to jumbo jets. According
to the definition of nanotechnology given earlier, any technology that manipulates matter
on a nanoscale, including ‘‘top-down’’ techniques, can be denoted as nanotechnological.
As ‘‘top-down’’ and ‘‘bottom-up’’ nanoscale designs have reached the point where the best
achievable feature size for each set of techniques is approximately the same [16], it is
natural to expect that the encounters of these two design systems at nanoscale will result in
nanoproductivity that will mark a new era.

3.2. Hard-tech approach and soft-tech approaches

In the overall ‘‘bottom-up’’ R&D trajectory that leads to future designs and applications
of nanotechnologies, two general pathways can be defined. The first is a hard-
tech approach [17], which pertains to the use of massive and complex apparati to induce
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atom-by-atom or molecule-by-molecule manipulations, and organize relatively simple

building blocks into applicable nanostructural outcomes. The second is the soft-tech
approach, which includes the design of complex building blocks via self-assembly by
performing manipulations on a macroscopic scale [18]. This approach uses relatively
inexpensive and commonly accessible equipment that might—contrary to the hard-tech
approach—naturally induce decentralization of power and sustainable proliferation of
practical knowledge. Basic research, which lies at the root of every successful development
and transfer of advanced technologies in a global society [19], prospers from the use of the
latter perspective. The hard-tech approach to the design of nanoproducts typically ignores
natural limits and pathways, and imposes anthropocentric purposes on natural substrates.
However, the soft-tech approach also lacks the ability to consciously organize synthesized
building blocks into processed functional appliances. Nevertheless, optimism continues to
flourish regarding the possibilities of the molecular machining approach to nanodesign [20]
and the potential to self-organize relatively large and complex structures into hierarchically
structured outcomes [21].
While the ideal of ‘‘everything is possible’’ dominates the hard-tech, manipulative
approach to the birth of atomically assembling nanotechnologies, a more modest attitude
is typical of the self-organizing methodology for designing nanosystems. As Richard
Smalley, Nobel Laureate in chemistry and a proponent of soft-tech, puts it:

Much like you can’t make a boy and a girl fall in love with each other simply by
pushing them together, you cannot make precise chemistry occur as desired between
two molecular objects with simple mechanical motion along a few degrees of freedom
in the assembler-fixed frame of reference. Chemistry, like love, is more subtle than
that. You need to guide the reactants down a particular reaction coordinate, and this
coordinate treads through a many-dimensional hyperspace. [22]

However, the proponents of a more manipulative, mechano-synthetical approach to the

formation of functional nanostructures do not insist that everything is possible. They
maintain:

The principles of MNT [molecular nanotechnology] involve no new basic science,

only new applications. Its development, like the Moon-landing program or any
innovative engineering project, will require considerable trial and error learning—
that is, many routine, incremental scientific discoveries. Its development will require
hard work, but not scientific breakthroughs [20].

This leaves the impression that the limitations of fundamental physico-chemical laws
will, through trial-and-error, ascertain what is possible to achieve and what is not possible
[20].
Contemporary scientific aspirations to construct nanosized assemblers that can
synthesize practically everything in an atom-by-atom fashion are, to a large extent,
analogous to the idea of Laplace’s demon, which marked the era of enlightenment.
Similarities can be perceived between the former idea of the possibility of mechano-
synthesizing everything and the latter idea of the possibility of constructing a computer
which, preloaded with the complete set of initial boundary conditions of all the particles of
the world and deterministic equations that define their movements and interactions, would
be able to calculate and predict any future event throughout space and time.
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However, two features of the man/nature relationship prevent these aspirations from
achieving reality: size and complexity. Measuring all the initial parameters of any slightly
complex natural system, and calculating all the necessary sets of equations, would require
enormous amount of time. Likewise, assembling nanoproducts atom-by-atom would
require impractical amount of time. As crude comparisons, a single teaspoon of water
(similar in size to a device that could establish communication between a human user and
nanosized information) has approximately the same number of water molecules as there
are teaspoons of water in all of the Earth’s oceans [23]; or the ratio of one nanometer to the
human head is approximately equal to the ratio of the human head to the planet Earth
[24]. Future states of natural systems, where every systemic component changes with every
other over the course of time, are impossible to predict due to non-linear interactions that
govern the relations between inherent systemic variables. Similarly, the complexity of the
supra-molecular, hierarchical organization of any nanodevice significantly limits the set of
possibly attainable nanoarchitectures. The effects of thermal fluctuations and probabilistic
quantum effects at the nanolevel (including hydrogen bonding for some chemistries [25]),
as well as the complex environment of chemical reactions that tend to be induced by
nanobots [26], may naturally limit the potential set of achievable nanostructures as well as
the perfect reproducibility of nanoscale construction.
It has been argued that in order for a chemical reaction to occur not only do directly
interacting entities need to bump into each other, but also the overall spatial context of the
reaction to be initiated must be precisely set in order to obtain the desired outcome [26]. If
a scientist hoped to solve this problem by introducing more than one manipulating tip for
each entity (or relatively small cluster) near the reaction site, then he/she might realise that
there is not much ‘‘room at the bottom’’ as Richard Feynman argues [17]. Achieving
balance between vision of absolutely desirable order and natural randomness results in
harmony between order and chaos—typical for every biological organization in nature.
The larger question is whether future nanodesign can transcend this compromise, which
today seems like an inescapable natural necessity.
The paradigm of objective realism, as seen through the philosophical interpretations of
quantum theory [27,28] and biologically founded constructivist philosophies [29–31] or
complexity science [32,33], is a convenient system for organizing knowledge but not a
foundation for a comprehensive worldview. All the results of human perception might be seen
as interplay between the domains of subjectively interpretative and objectively representative
qualities. Inseparable ontological features of the natural world, and interpretative,
epistemological spheres of human experience together produce all the perceptive outcomes
that stand at the end of every measurement process and at the beginning of each scientific
conceptualization. The relationship between nature and man can thus be viewed as preeminent
in everything, and approaches to materials and nanotechnological design are no exception.
Through the self-organizing approach to nanoengineering design, the doors to steward-
ship of natural paths open. Contrary to the shallow approach (instigated by proponents of
the hard-tech, manipulative, socially and ecologically decontextualized design) according to
which an epithet of ‘‘natural’’ is deserved for all endeavours that do not violate fundamental
physical laws of nature, a more profound outlook towards nanodesign is created. According
to that outlook, only with innovations that preserve the natural diversity of relationships in
the living domain can truly long-term creative endeavours be sustained. The design of
materials with respecting spontaneous, self-organizing pathways in nature will lead us to
nanotechnologies that truly go hand-in-hand with nature.
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With the rise of inventions that accommodated nanostructured materials, most

applications were—due to high surface areas of nanoparticles—based on their catalytic
activities [34]. However, with the advent of precise nanotectonical manipulations (either
using self-assembling systems or ‘‘top-down’’ control), nanomaterials started to find their
way into new areas such as electronics, information technology (IT), biotechnology, and
medicine [35]. Many ideas focused on how to revolutionize virtually every modern industry
by introducing innovative nanosensitive appliances. Coupling self-organizing production
of uniform nanosized particles with methods for assembling such multi-atomic units into
functional suprastructures offers an elegant way to obtain ultra-fine devices. However,
there is still some question as to whether an enormously complex environment similar to
cellular interiors would be necessary to achieve that aim. The spontaneous assembly of
dispersed atoms on a specific substrate into clusters with precisely defined aggregation
numbers and geometries [36] could be a useful starting point.

3.3. Trial-and-error approach

It is exceedingly difficult to predict the outcomes of experimental settings that aim to

produce new nanostructures and morphologies; indeed, the best results in today’s practical
nanoscience come from trial-and-error approaches. There is considerable evidence that slight
changes in the condition in experiments of nanoparticle synthesis will produce significant
differences in the end results [37]. For instance, replacing manganese ions with nickel ions in
an experiment of reverse micellar precipitation synthesis of mixed zinc-ferrite resulted in the
production of spherical particles in the former case [38] and acicular particles in the latter
[39,40]. When the synthesis of copper nanocrystals was performed in the presence of NaF,
NaCl, NaBr, or NaNO3, small cubes, long rods, cubes, and a variety of shapes resulted,
respectively [34]. The choice of precipitation agent within in situ preparation of nanoparticles
in solution can often result in distinctive morphologies [41,42]. When bromide ions of
cetyltrimethylammoniumbromide (CTAB) surfactant in a particular wet synthesis of barium
fluoride nanoparticles were replaced by chloride ions (CTAC), the product’s identity was no
longer the same, whereas the replacement of 2-octanol by octanol significantly modified the
crystallinity of the obtained powder [43]. It has been found that even stirring an aging
solution where synthesis reactions take place can have a decisive influence on some particle
properties. Thus, using a magnetically coupled stir bar during the powder’s aging time
influenced crystal quality, and, in some cases, resulted in a different crystal structure as
compared with non-magnetically agitated solutions [44]. In case of the synthesis of organic
nanoparticles in reverse micelles, the use of a magnetic stirrer led to the formation of larger
nanoparticles compared with particles obtained using ultrasound bath as a mixer, even
though no changes in particle size were detected with varying solvent types, microemulsion
composition, reactant concentrations, and even geometry and volume of the vessel [45].
Changes in size of volume in which the reactions of nanoparticles synthesis take place
(as occurs when the transition from small-scale research units to larger industrial vessels is
performed) can result in dramatic variations in some essential properties of synthesized
materials [46]. Also, when the same chemical procedure of nanoparticles preparation was
performed in closed and open otherwise identical vessels, perfectly uniform spherical
particles were produced in the former case but elongated particles of similar narrow size
distribution were produced in the latter [46]. Complex modern synthesis pathways
(as opposite to relatively simple traditional, solid-state routes) offer unlimited potential
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for each desired chemical compositions. Attractive morphological, microstructural, and

hierarchical structural arrangements can be obtained by unexpected and unpredictable
starting and limiting conditions during synthesis experiments.
In each creative research design, special attention is given to the boundary that separates
and links the domains of what is known and possible on one side, and unknowable and
impossible to know or obtain on the other. However, discerning unknowable and
unattainable from generally impossible to achieve is never easy. Some limits, such as
superparamagnetic limits recently overcome by preparing ultra-small but highly crystalline
and supra-organized Fe–Pt particles [47], are there to be surpassed. Other limits, like
Heisenberg’s uncertainty principle or the laws of thermodynamics, are impossible to
transcend. Meta-uncertainties, i.e., uncertainties about uncertainties, present a necessary
first step in creative extensions of ‘‘possible–impossible’’, ‘‘known–unknown’’, ‘‘predicta-
ble–random’’ boundaries of human knowledge. They are reflected in ever more diverse and
mutually developing risks and opportunities, dangers and benefits. New technologies never
perfectly solve certain problems they aim to fix, but they do expand the potential options
for risks and benefits, keeping them in creative balance, and thus fostering an unending
search for innovation and advancement through problem solving.

4. Ecological advantages and risks

Although most new technologies aim to solve certain problems, they also carry risks
related to their unpredictable effects on the sensitive systemic variables of the environment
[48]. As a rule, the more prosperous a technology appears, the more unpredictable
consequences and potential dangers it may entail. Therefore, both sides of a new
technology—that is, its beneficial development and the possible negative consequences—
should be investigated in parallel. Of the US$710 million spent in 2002 by the US government
on nanotechnology research, only $500,000 was spent on environmental impact assessments,
despite the fact that new materials were a major part of the product pipeline [49].
Many of the favourable ecological features derived from nanotechnological production
come hand-in-hand with fears arising out of the uncertainty or dangers of their
environmental effects and the possibility of losing control of increasingly destructive
functions of nanoproducts. The potential advantages of nanotechnologies include:

 Opportunities to produce devices that could select and reorganize atoms and molecules
of the biosphere with the aim of remedying unbalanced environmental relationships.
 The possibility of preparing technological products in a ‘‘bottom-up’’ style without
producing wasteful and dangerous by-products, as typically occurs with most of today’s
current manufacturing processes.
 The ability to produce more functionally efficient materials and devices with higher
strength-to-weight ratios. These could eventually eliminate the need for massive
infrastructural power generation systems, stimulate the introduction of renewable, more
efficient energy sources, and lead to a reduction of human ecological footprints [50].

Several disadvantageous effects of nanotechnologies also exist.

 It is possible that self-replicating nanobots could (in an extreme case) either aggressively
[51] or through slowly rising supremacy [52] wipe out the whole biosphere.
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 A more realistic scenario of unsustainable applications of nanoproducts could further

destabilize the already endangered diversity of the biosphere.
 They could further extend the existing gap between rich and poor.

Because the development of nanotechnologies is only in its infant stages, predictions of

both opportunities and dangers are profuse. Predictions typically fail to match reality, as
occurred in predicting the influence of diverse micro-, nano- or liquid-composed chemical
substances on the environment. According to the well-known cautionary principle, which
states that ‘‘the lack of certainty, given the current scientific and technological knowledge
shall not delay effective and proportionate actions to prevent hazards’’ [53], the inability to
grasp the whole spectrum of the effects that certain technologies will pose to the
environment should not retard efforts to research the possible harmful effects of
nanotechnologies before they are introduced to the biological world. Unlike the case of
asbestos chemicals (when the span between knowledge of its harmful effects and the
introduction of internationally accepted standards of use lasted approximately a century),
all indicators of adverse side effects of nanosystems should be carefully considered, even if
this process slows down the pace of technological innovation.
As technology develops and society evolves, regulatory approaches to environmental,
legislative, cultural, and ethical issues must keep pace. Neither an immediate moratorium
[14,55] on the release of new nanoparticles nor clinging to an old set of existing regulations
conveys the right attitude. However, a creative balance between innovation and regulatory
precaution can be achieved. While gaps between science and ethics may occur, they can be
bridged through the promotion of multi-disciplinary decision-making processes that
include humanistic and ethical guidance of nanodesign [56].
Nanosized particles are more biologically active compared with micron-sized particles of
the same chemical composition owing to their greater surface area. Nanoparticles can be
used in modern biomedicine treatments in a variety of useful ways: MRI contrast
enhancement; hyperthermia treatment [59,60]; drug delivery and targeting [61–63];
magnetic separation, protein detection and purification [64]; magnetic field-assisted
radionuclide therapy [65]; magneto-relaxometrical diagnostics and eye surgery [65]; the
detection of intracellular molecular interactions [66], with the possibility of developing
gene and/or cellular metabolic therapy [67]. Concerns about the possible adverse health
effects of nanoparticles include the relative persistence (i.e., several months) of
nanoparticles in lung tissue; their potential to pass the blood–brain barrier, to reach
brain tissues [57] and induce damage [11]; and their absorption through the skin into the
bloodstream [58] via uptake into lymphatic channels. Potential for both inflammatory and
pro-oxidant activity on one side, and antioxidant activity on the other has been ascribed to
nanosized particles. Although nanoparticles are ubiquitous in ambient and indoor air, in
fact they have been present in the environment since the earliest stages of evolution [68].
In a set of toxicological experiments, polytetrafluoroethylene (PTFE) particles with sizes
of 20 nm proved lethal upon inhaling, whereas 130 nm sized PTFE particles did not
produce any ill effects in the breathing air [48]. These results indicate not just the increased
harmfulness of smaller particles but also the fact that a slight change in size becomes
significant when evaluating potential toxicity relative to living organisms. Another study
concluded that in low concentrations of inhaled nanoparticles, when the biological uptake
processes on the surface of the cell were faster than the physical transport to the cell, the
smaller particles were, due to high density, fastest to agglomerate, whereas the larger
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particles stayed mostly unagglomerated and more resistant, and required more time for the
body to discard [69]. The familiar case of thalidomide, which was ‘‘proved’’ to be harmless
to animals but found to have tragic consequences for pregnant women, shows that benefit
in one context could mean harm in another. It is therefore impossible to know or predict
the overall effects on the environment of any chemical, and premature generalizations of
either great harm or complete safety regarding the introduction of nanomaterials and
nanotechnologies must be made with great care [70].
Particles in new environmental surroundings will create new behaviours that are often
difficult to predict. Fine particles in the atmosphere are located primarily near the earth’s
surface and usually covered with layers of adsorbed water, which increases their catalytic
features already promoted by large specific surface areas [71]. Nanoparticles can travel
much greater distances by air or in water comparing to microparticles [13]. Various other
chemicals are almost equally distributed among the organisms in the biosphere [72], and
wide ecosystemic distribution of industrially produced nanoparticles could be expected.
Even though the properties and impacts of raw or intermediate materials used to produce
nanomaterials might be well known from a risk assessment perspective, the safety risks
during manufacturing and the environmental fate of nanomaterials cannot be foreseen
with certainty. Despite this, by learning from the experience of previous industrial
production, nanotechnologies today have an unprecedented opportunity to evolve into a
‘‘green’’ industry [73].
Due to the enormous complexity of the environment today, it is exceedingly difficult to
reach definitive conclusions about the overall effects and consequences of certain materials
or technologies on the environment. For example, concerns about the harmful effects of
the sun’s UV rays have for some time been resolved by the invention and dissemination of
sunscreen agents. However, despite the fact that their use reduces the risk of sunburn, it
has never been proved that such use prevents skin cancer in humans. Recently, some have
suggested that the use of sunscreens may actually increase the risk, allegedly due to organic
chemicals and photoactive particles such as titanium dioxide, which when nanosized can
easily penetrate the skin and potentially generate free radicals that might disrupt healthy
DNA sequences [16]. Knowing that humans are an extremely adaptive species in the
context of the biosphere [74], and that trial-and-error has always been part of evolutionary
R&D, feedback-sensitive efforts to resolve any inharmonies in the organization of life
should present mechanisms for advancing society on the scientific, ethical, and
technological levels.

4.1. A comparison with the case of genetically modified foods

Even though the products of biotechnology may present ecological dangers that are
more difficult to manage [54], as nanoproducts move from research laboratories into the
marketplace it will be necessary to develop precise standards to evaluate the spectrum of
their ecological effects. Although this spectrum can never be perfectly projected, the goal
should be to study the widest possible range. James Watson has recommended that 3–5%
of the funds allocated to bioengineering should be devoted to the study of ethical, legal,
and social implications [56].
The case of genetically modified (GM) foods offers a recent and still developing case of
the challenges and social impacts that face nanoscience and nanotechnology on their way
into industries and markets. Both GM foods and the Human Genome Project have
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contributed to discrepancies between scientific and public opinion. The widespread

rejection of GM foods occurred as a result of ethical and social consequences, and it would
be well to avoid similar situations as nanotechnologies become an increasingly significant
market force.
The primary reason for the breakdown of public trust in GM products did not initially
arise from public perceptions of health and environmental hazards or impending
catastrophes but instead through rash pronouncements and heavy promotion of GM
foods and products by large corporations, later shown to be at the expense of broader
public interests. The most important lesson from the case of GM foods is that uncertainties
should be openly acknowledged. Wide-ranging, inter-disciplinary discussions that include
public voices, leading to shared responsibilities and more careful choices, are approaches
that acknowledge public attitudes and values and lead to more sustainable solutions. ‘‘An
ability to accept uncertainty—to say ‘we’re not sure’—is an essential component of this
new approach’’, says James Wilsdon, a proponent of the decision-making approach that
does not rely on pure technical criteria alone but strives to take into account as many
diverse societal perspectives as possible [13].
Risk assessment of nanoproducts should also follow a direction that ensures that the
savings in resource consumption during usage are not offset by increased consumption
during manufacture and disposal. And the more ‘‘upstream,’’ culture-friendly, purpose-
driven, and wise perspectives should not be disregarded in favour of ‘‘downstream’’, more
immediate anthropocentric risks and consequences. As part of this approach, the
nanoscience research centre at Cambridge University has appointed a lab-based social
scientist to focus on the reflection of social values and needs in real-time research practice
and guidance [13].
The question of compromise between novelty and incrementality still persists as an
important dilemma within nanotech policy. Unlike the case of GM foods, when novelty was
insisted upon in order for patents to be granted, but when questions about safety regulations
were put forth, substantial equivalence with natural counterparts was claimed, similar
tendencies ought to be met with caution, knowing that every nanomaterial and nanoproduct is
unique and should not be smuggled down the regulatory pipeline under the guise of generalized
etiquette. Since potential damage to humans does not come directly through digestion or
contact with GM foods but instead through disrupting naturally diverse ecosystems, a
regulatory eye should always be maintained not only on narrow and short-term frames of
reference but also on wide-context and long-term influences on the biosphere as a whole.

4.2. Sustainability and harmony with nature

Sustainability of nanotechnological methods for the production and functional

implementation of nanoparticles presents another major ecological concern. In nature,
permanent waste does not exist since waste produced by one species is absorbed as food by
others. In contrast, contemporary industrial production processes routinely produce long-
term, non-biodegradable wastes. In this sense, the principles of ‘‘green chemistry’’ [75]
provide useful guidelines [76–78] for modifying today’s synthesis processes into one that
are more sustainable and less waste producing. An orientation towards combining
production paths into symbiotic organizations of both small-scale and large-scale
production sizes, which could result in zero-waste industrial environments, has been
proposed [79–81] as an inspiring possibility on the horizon.
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Many aspects of estimating the viability of methods and procedures for preparing
nanostructured materials, and their eventual organization into supra-molecular, multi-
hierarchical structures, should be taken into account. Ordinary physico-chemical analyses
should not be the end points of such investigations; consideration should also be given to
economic, ecological, and socio-ethical perspectives, including the influence of nanopro-
ducts, the effects of synthesis pathways, resource supply, and the fate of by-products on
relevant environments.
Since self-replicating nanomachines—the final frontier of the development of
nanotechnoscience—tend to copy natural design (namely, the functionality of cellular
structures), there are many questions that can be posed concerning the harmonization of
nanoscience with nature. For example, if nature never produces absolutely identical
entities in its design and self-replication processes (and we have learned that mistakes in
replication processes are key to the evolution of life), are tendencies towards perfect
uniformity and reproducibility in today’s structural design procedures in harmony with
nature? How can man produce perfection via imperfections, as nature does? If nature relies
on non-linear systems in which every subsystem changes according to overall changes in
the system, should purely top-down, linear, and unilateral hierarchical organizations in
human products design cede their places to circular, decentralized, and more feedback-
oriented systems?
Popular visions of limitless nanotech possibilities are inconsistent with the finity of
natural organizations and earth’s resource base. The contemporary problem of population
congestion on the planet is on a collision course with an oft-mentioned desire to cure all the
world’s illnesses by applying special nanobots in biomedicine treatments that it is hoped
would extend man’s lifespan. On the other hand, subtle and long-term changes induced in
individual organisms in the presence of potentially toxic substances, are exceedingly
difficult to spot and discern from other environmental influences. The lack of evidence
concerning the negative health effects of nanoproducts on humans, animals, and/or cell
cultures should not be regarded as a sign of their eco-friendliness. Given the impossibility
of defining with absolute accuracy the range of effects that certain substances may have on
the environment, perhaps all resulting safety announcements should be enclosed within the
frame of reserved uncertainty. Human civilization is supported by an inconceivably
complex organization of life, and the study of the effects of nanoproducts and
nanotechnologies on this foundational web of biological and ecosystemic relationships
should not be underestimated for the sake of anthropocentric evaluations of narrowly
schematized health effects of nanoproducts on human beings.
Natural design processes are typified by the use of (a) relatively simple building blocks;
(b) complex environments and complex processes; (c) parallel processing (hundreds of
reactions at a time); (d) relatively slow attainment of end states; (e) dealing with sub-
picomolar quantities; and (f) imperfect reproducibility (overcome by high selectivity for
products that meet the required specifications) [82]. By comparison, synthetic methods in
chemistry are typified by (a) the use of relatively complex building blocks; (b) simple media
and processes; (c) linear reactivity (one reaction at a time); (d) quick attainment of end
states (due to far-from-equilibrium conditions); (e) dealing with molar quantities; and (f) a
tendency to duplicate reproducibility. Therefore, since natural design and nanoengineering
are often regarded as a single organization of creative efforts [83], fundamental biomimicry
represents a complex but enormously fruitful challenge for today’s materials science and
engineering. Nearly impenetrable abalone shells, flexible and patchy butterfly wings, spider
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threads more rigid than steel, unwettable and self-cleaning lotus leaves, and the skin of
dolphins are some examples of products of natural design prepared not by conscious
manipulation but by spontaneous, self-organizing processes of nature—and still without
comparable counterparts in any laboratory.
It has been suggested recently that the only way to solve the so-called ‘‘fat and sticky
fingers’’ problem [26] of molecular assembly design is to establish structures reminiscent in
functionality of enzymes and rybozomes. However, water is a necessary precondition for
such an organization. This does not mean that the fields of bioengineering and
nanotechnologies will not some day merge, or that we will eventually learn that along
the technological route to improving quality of life and understanding nature, we have
been in fact always trying to create or meet something that already exists, namely, our
beings and the deepest qualities of life. Thus, humans—after more than four billion years
of evolutionary trial-and-error R&D—may be the ultimate nanomachines [84].
In any case, while every novel breakthrough technology normally draws on traditional
underpinnings (which through redeployment in a new context acquires new meaning [85]),
design visions should naturally move from obscure mechanistic and violent military
metaphors towards functional notions that better match the natural order of things [24]. If
nanoscience is a trans-disciplinary heading that is evolving into a specific scientific
discipline, then holistic, networked, and self-assembled imagery might serve as its
paradigm [21,86], in contrast to the manipulative and realistic imagery of the
contemporary disciplines of physics, chemistry, and engineering [85].

5. The quality of scientific research

Whereas academic researchers were generally free from external direction until the
beginning of the 1970s, the past 30 years has seen a continued increase in R&D investments
and an ongoing decrease in global per capita economic growth [87]. Limiting research
creativity within the scope of rigid, preconceived objectives, or the pressure to publish in
peer-reviewed journals, combined with vague evaluations of the quality of research
proposals and project results, have gradually moved aside the sense of personal research
responsibility, and may influence the unfavourable drift of research. Conforming to trends
that lead to career establishment, instead of focusing on the long-term viability of striving
in the largest context of the organization of life, represents the greatest danger in the
contemporary scientific society. Animating a sense of responsibility that refers not only to
higher authorities but also to deeply rooted ethics within is the major challenge to creative
enhancement and truly careful design of modern technologies.
Some of the most important steps in the evolution of science, including the discoveries of
quantum mechanics, the theory of relativity, and molecular biology of the twentieth
century, were not derived from market needs, external demands, or predetermined techno-
scientific objectives. Rather, many steps came as acts of divine, inwardly turned inspiration
from which inexhaustible sources of cognitive, technological, and informational
enrichment were found decades later. It has been argued recently that most of the major
scientific breakthroughs in the history of science evolved from very little or no funding [88].
But as any researcher knows, it is impossible to directly use the laws of nature to produce a
desired object; all that can be done is to set the right limiting conditions and let nature play
the recombination part, after which collection, analyses, and further use of outcomes take
place. Every process of material and technology design is to some extent self-organizing.
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The fundamentals of nature are never touched; instead, just the tracks upon which her
trains are already heading are manipulated.
Besides its inner, inherently problematic side, scientific research has its outer, applied,
social, and humanistic side as well. The R&D part of scientific work is only one side of the
bridge over the river of knowledge; the other side reaches toward the shore of human
needs. So one coast of these scientific waters contains the grounds of fundamental physico-
chemical laws of nature upon which research products are being built; on the other coast,
the R&D bridge brings products to society. However, in converting research dreams to
reality, the bridge represents a path often named ‘‘nightmare’’ or ‘‘valley of death’’ [89,90],
due to its inter-disciplinary, widely contextual character filled with puzzlement, doubt, and
risk during the effort to bring R&D creations into social, economic, and ecological
daylight.
As the laws of nature are never entered into (in the sense that they are never used directly
and intentionally in applied scientific design), direct research objectives should to some
extent cede their place to open, so-called ‘‘blue skies’’ research [87]—free from externally
imposed constraints. On the other side, an orientation towards profitable returns in the
market ought to be replaced by a belief that as products are being obtained via self-
organization pathways, setting them into social and economic environments will ensure
that they find fertile ground—provided they present truly pragmatic, eco- and user-friendly
products. In the field of nanoscience, this means that diving into nature’s wonders, and a
profound devotion to understanding natural order on a nanoscale, represents the
appropriate attitude for fundamental development of future nanotechnology designs.
Basic scientific research is oriented towards gaining a fundamental understanding of
nature as essential for advancing science and technology forward. When combined with a
trial-and-error approach in materials design, every research result becomes equally
important to the scientific mind. The importance of trial and error within nanodesign
implies that mistakes and ‘‘not-how’’ are as vital as ‘‘know-how’’ on the road to advancing
the conceptual network of nanosciences. Every small research, regardless of its immediate
or near-term success, stands as an enormously significant potential source of knowledge
advancement and innovative achievement.
It is my opinion that acknowledging uncertainties in areas where the development of
nanoproducts takes place, together with respect for self-organizing natural patterns, offers
a far more harmonious plan for unfolding nanoscience and nanotechnology. The truly
valuable fruits of human hardships are never immediately seen, often remaining just out of
sight beyond the horizon of actual view. Therefore, the tendency of mainstream science to
quickly sell nanotech to the financial community, and to collect money from proposed
ideas and hoped-for nanodreams, should be undertaken with extreme care and
deliberation. The nanotech areas of greatest scientific uncertainty, such as the toxicology
of nanoparticles and basic, not-immediately-practical innovations, should not be exempted
from funding, even though there is currently only about h5 billion of total global
investment in nanotechnologies (with h2 billion coming from private sources) [16] devoted
to them.
At least 35 countries currently have some kind of national nanotech research
programme [14] and, based on experience in the IT field, it has been extrapolated that
nanotechnologies have the potential to create seven million jobs in the global market by
2015 [91]. The US National Science Foundation (NSF) predicts that nanotechnology will
be a US$1 trillion market within 6–7 years [92]. At the same time, the NSF, while spending
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$8 million on nanotech projects, did not fund a single project that focused on societal
implications of nanotechnologies [56]. Whereas citations in scientific databases on
nanotechnology follow an almost exponential line of growth, the number of citations on
ethics and societal implications shows an almost negligible increase [56]. Since a single
nanoscale innovation can span the fields of pharmaceuticals, paints, food, textiles, sports,
electronics, telecoms, automotive, and other industries, trans-disciplinary scope and
decisions that do not come from strict experts’ views need to be given serious
consideration. Areas of current research in self-assemblying syntheses, computational
and supramolecular chemistries, genetic and protein engineering, and the scanning-probe
manipulation of atoms and molecules need to be intertwined in order to achieve more
significant, sustainable progress in developing future nanotechnologies [22]. Only through
fostering multi-, inter-, and trans-disciplinary approaches to organizing man’s knowledge
and directing programmes of research, can we find the way to nanotechnologies that are
inexpensive, sustainable, culture- and eco-friendly, collaborative, freely accessible, and
‘‘open source.’’

6. Conclusion

After studying well-known pathways from new perspectives, insight into new qualities is
growing and wiser returns to old paths may be expected. Such is the nature of multi-
disciplinary approaches to problem solving. By stepping out of the rigid paths being
followed, better views of the destinations can be established. Otherwise, the danger
remains that we might stay locked in a ‘‘blind spot’’ where we do not see that we do not
see. The first step towards improving our knowledge is to see that we do not see—the
major point of this paper.
Numerous impossibilities, uncertainties, and unknowns within research areas of
nanomaterials, nanosciences, and nanotechnologies were discussed. Examples of changes
in the initial conditions of experimental observations, which can lead to significant
differences in measured outcomes were outlined. I highlighted the complexity of the many
environments within which nanosystems appear today. All generalizations concerning
their effects on the corresponding media, therefore, need to be taken with special care.
Advances in extending mankind’s knowledge and predictability in uncharted territories
have been continually present since the word ‘‘nano’’ first appeared in the context of
materials science. However, we should be firmly assured that prediction impossibilities,
indeterminacies, and ‘‘horizons’’ will remain in the organization of our knowledge. Our
work should not be directed towards erasing the unknown by premature generalizations,
but instead towards carefully walking the endless line where the coasts of the known and
the sea of the unknown meet.
Careful guidance in the development of nanotechnologies provides opportunities to
spontaneously replace human superimpositions on natural ecosystemic substrates with
more harmonious, responsibly feedback-permeated patterns. It was Paul Tillich who said,
‘‘Nature draws straight with curved lines,’’ referring to the well-known fact that natural
self-sustaining processes follow non-linear patterns with holistic features [93–95]. In this
work, I have described the missing links in a closed loop that connects nanomaterials
structures and properties with procedures of placing nanomaterials and nanotechnologies
in biological domains and in the context of the overall biospherical web of life. The
favourable feature of any cyclical dependency is that taking action on any of their linking
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parts may influence a more harmonious overall flow. It has been acknowledged that
searching for the foundations of chemistry led us to the principles of physics. The search
for the foundations of physics ends with philosophical discussions that, due to the
biological basis of our cognitive apparati, bring us to biological principles. Yet, their
detailed considerations turn us to chemical pathways—the beginning of our journey.
This work could end with an ancient oriental tale [96] about a stonecutter, as a clever
allegory of the circular arrangement of the areas of scientific and humanistic interest in the
development of nanomaterials, nanosciences, and nanotechnologies, and of the cyclical
pattern of materials and technology design. In the story, a stonecutter, dissatisfied with his
life, searches for the fundamental founding principles of life. He becomes the sun first,
impressed by its shining constancy. After a time, he realises that clouds can block the sun’s
rays. So he changes his mind to become a cloud. Then he realises that clouds are moved
too, by the force of wind, so, he decides to become wind. After enjoying being wind for
some time, he notices that there is a stone that cannot be moved by his enormous strength,
and the man decides to become a stone. Thinking he had finally found the firmest
foundation of life, he realised that even then he could be changed by human hands. He
turns to them and reveals that it is himself, the stonecutter, who should have always been
the most appreciated doer in the creative world.
As in this allegory, the design of modern materials and technologies through wise
consideration of a wide range of effects on intertwined scientific and humanistic disciplines
should become a wonderful story of informative and cognitive enrichment.

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Vuk Uskoković was born in Belgrade, Yugoslavia. He earned a B.Sc. degree from the Faculty of Physical
Chemistry at Belgrade University in 2001, and in 2003 was awarded an M.Sc. degree in advanced materials and
technologies from the University of Kragujevac, Serbia and Montenegro. From 2002 to 2006, he was with the
Advanced Materials Department of the Jožef Stefan Institute, Ljubljana, Slovenia. He received a Ph.D. degree
from the Jožef Stefan International Postgraduate School of Nanosciences and Nanotechnologies in 2006. As of
April 2006, he has been with the Center for Advanced Materials Processing of Clarkson University, Potsdam, NY.
Besides his devotion to scientific research, he has published shorter works and books comprising discussions that
combine the areas of scientific epistemology, ethics, ecology and sociology, with the aim of improving the
understanding of current problems in contemporary societies.