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Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Proceedings of the Trans-Disciplinary
Innovation Program (TIP) 2016
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Proceedings of the Trans-disciplinary Innovation Program
2016 (TIP16), at the Hebrew University of Jerusalem.
Edited by Elishai Ezra Tsur
Language editing: Maya Borisov
Full book is available in:
http://transdisciplinary-innovation.com
© HUstart - Entrepreneurship Center of the Hebrew
University of Jerusalem
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Advisory Board
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Andrey Eskin , Russia; Anthony Weil, France
Becky Wong, Hong-Kong; Catarina Papa, Brazil
Chen Mor, Israel; Daniela Klaiman, Brazil
Ernesto Ferreira, Brazil; Inbal Levi, Israel
Lital Friedman, Israel; Marcelo Lopes, Brazil
Mariana Fonseca, Brazil; Miriam Chen, Taiwan
Palak Dudani, India; Raymond Harari, Panama
Sebastián Chimal, Mexico; Shachar Schidor, Israel
Vanlu Madarame, USA; Yael Levinson, Israel
TIP16 Fellows
A group photo with
Astronaut Dr. Jessica Meir
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Chairperson Perspectives
Prof. Yigal Erel
Director Perspectives
Dr. Elishai Ezra Tsur
Special Article: Right and Wrong in AI
Dudu Mimran
Fellows academic papers in the Bioengineering track
Fellows academic papers in the Computer-vision track
Fellows academic papers in the Cyber/Data track
Transdisciplinary research projects
Final projects
Table of Contents
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
“The traditional view of creativity is that it is unstructured and doesn’t
fo!ow rules or patterns. That you need to think “outside the box” to be
truly original and innovative….. You should start with a problem and
then “brainstorm” ideas without restraint until you find a solution.
That you should “go wild” making analogies to things that have nothing
to do with your products, services, or processes. That straying as far
afield as possible wi! help you come up with a breakthrough idea. We
believe just the opposite. We’! show you that more innovation— and
better and quicker innovation— happens when you work inside your
familiar world (yes, inside the box) using what we ca! templates.”
Boyd et al. 2014
A burgeoning global population and demand for ever-higher
standards of living are placing enormous stress on the natural
world. Humanity today faces unprecedented challenges.
Climate change, energy and resource depletion, habitat loss,
invasive species, pollution and other types of environmental
degradation are forcing us to rethink our existing coping
mechanisms. There is no doubt that new directions in research
and technology are needed if we are to ensure our children’s
tomorrow. We strongly believe that to tackle these big
challenges in dramatically new ways, a transdisciplinary
approach is needed. We would like to provide an academic
environment in which our students, together and
independently, are able to think and develop new partnerships
Dean, Faculty of Science; 

Geochemist, The Fredy and
Nadine Herrmann Institute of
Earth Sciences;

The Hebrew University of
Jerusalem
Chairperson perspectives
Prof. Yigal Erel
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
in entrepreneurship that cross professional lines. We do not
know where our attempt will lead us in the future. We do know
that by creating an environment that fosters the exchange and
dissemination of ideas within our campus, exciting
technologies will emerge. By systemizing and structuring
transdisciplinary approach, the TIP program of the Hebrew
University will be providing a springboard that will position its
students well in the competition for external resources. More
specifically, we at TIP are trying to enlarge your box, enlarge
your tool kit and improve your ability to work as a team
member benefiting from the expertise of all members of the
team in order to come up with innovative ideas to social and
technical problems.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
The architecture of knowledge has been an integral part of
philosophy since the dawn of human thought. It has been
articulated, refined and reorganised throughout history, its
progress reflecting the progress of the human- driven will,
which began with the quest for truth, continued through the
pursuit of profit, and on to the aspiration for innovation.

The first reformation of the structure of knowledge was the
transition from Plato’s view on the unity of knowledge to its
discretisation, which began with Aristotle and peaked during
the industrial revolution. The unity of knowledge was broken
into artificial utilitarian elements and curiosity was replaced
with the will to produce refined materialistic value.
However, the more interesting upheaval of the architecture of
knowledge has occurred during the past few centuries. The
borders between elements became permeable and new bridges
were formed. Shreds of knowledge were connected and the
meaning of knowledge was once again transformed from
providing society with pure industrial value to attaining
innovation. It is a growing truth that great innovations are
characterised by a hyper-hybrid core: they are based on
increasing connectivity between disciplines. New revolutions
emerged, such as using micro-mechanical systems for high-
Principle Investigator, Neuro-
Biomorphic Engineering Lab,
JCT;

Program Director

The Hebrew University of
Jerusalem
Director perspectives
Dr. Elishai Ezra Tsur
A visualisation of the cross connectivity
of academic disciplines
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
throughput biological research and nuclear physics in medicine.
But constructing disciplinary bridges is not easy. Highly
detailed and technically intricate concepts had to be abstracted
to the point where they were truly democratised.
At the Hebrew University we often confronts the discretised
architecture of knowledge at that exact point. By promoting
abstract thinking, open-ended assignments and active student
participation, we teach advanced trans-disciplinary concepts
such as network analysis, signal processing, module-oriented
design and mathematical modelling to students of all
disciplines.
I suggest that a fourth revolution is upon us: a trans-
disciplinary revolution. While the current architecture anchors
objects of interest to multiple boxes of knowledge, the next
revolution shall set those anchors free. Concentrating on
curiosity and observations – rather than finding the right
anchor to stabilise us to known ground – can allow new
meaning to arise. Instead of the scattered concrete buildings
housing faculties of applied physics, chemistry or dance,
buildings for the study of the origin of life or alternatives to
monetary economy will be erected. Instead of classes in
physics, biology and history, children will be given a class on
the manifestation of consciousness. Students’ views will be
radically shifted from being trained to polish a small screw in a
great system, to taking an integral part in Plato’s vision of the
unity of reality and knowledge.
Trans-disciplinary learning also deals with classic dilemmas in
education. First, it faces the dissolution problem of the
disciplines of humanities by giving disciplines such as history,
ethics, philosophy and literature an important role. It also faces
the fact that knowledge today is abundant and that the role of
schools has to change accordingly by promoting curiosity and
teaching the way bodies of knowledge can be integrated into
new objects of beauty.
Specialisation is important, but it is not the only thing that
matters. Disciplinary boundaries can be dissolved to the point
where our challenges are reduced to modular design – where
curiosity becomes the meaning.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Background
The DARPA Cyber Grand Challenge (CGC) 2016
competition1 has captured the imagination of many with its AI
challenge. In a nutshell it is a competition where seven highly
capable computers compete with each other and each
computer is owned by a team. Each team creates a piece of
software which is able to autonomously identify flaws in their
own computer and fix them and identify flaws in the other six
computers and hack them. A game inspired by the Catch The
Flag (CTF)2 game which is played by real teams protecting
their computer and hacking into others aiming to capture a
digital asset which is the flag. In the CGC challenge the goal is
Special Article
Right and Wrong in AI
Dudu Mimran
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
to build an offensive and defensive AI bot that follows the CTF
rules.
In recent five years AI has become a highly popular topic
discussed both in the corridors of tech companies as well as
outside of it where the amount of money invested in the
development of AI aimed at different applications is
tremendous and growing. Starting from use cases of industrial
and personal robotics, smart human to machine interactions,
predictive algorithms of all different sorts, autonomous driving,
face and voice recognition and others fantastic use cases. AI as
a field in computer science has always sparked the imagination
which also resulted in some great sci-fi movies. Recently we
hear a growing list of few high profile thought leaders such as
Bill Gates, Stephen Hawking and Elon Musk3 raising concerns
about the risks involved in developing AI. The dreaded
nightmare of machines taking over our lives and furthermore
aiming to harm us or even worse, annihilate us is always there.
The DARPA CGC competition which is a challenge born out
of good intentions aiming to close the ever growing gap
between attackers sophistication and defenders toolset has
raised concerns from Elon Musk4 fearing that it can lead to
Skynet. Skynet from the Terminator movie as a metaphor for a
destructive and malicious AI haunting mankind. Indeed the
CGC challenge has set the high bar
for AI and one can imagine how a smart software that knows
how to attack and defend itself will turn into a malicious and
uncontrollable machine driven force. On the other hand there
seems to be a long way until a self aware mechanical enemy can
be created. How long will it take and if at all is the main
question that stands in the air. This article is aiming to dissect
the underlying risks posed by the CGC contest which are of a
real concern and in general contemplates on what is right and
wrong in AI.
Dissecting Skynet
AI history has parts which are publicly available such as work
done in academia as well as parts that are hidden and take place
at the labs of many private companies and individuals. The
ordinary people outsiders of the industry are exposed only to
the effects of AI such as using a smart chat bot that can speak
to you intelligently. One way to approach the dissection of the
impact of CGC is to track it bottom up and understand how
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
each new concept in the program can lead to a new step in the
evolution of AI and imagining future possible steps. The other
way which I choose for this article is to start at the end and go
backwards.
To start at Skynet.
Skynet is defined by Wikipedia5 as “Rarely depicted visually in
any of the Terminator media, Skynet gained self-awareness
after it had spread into millions of computer servers all across
the world; realising the extent of its abilities, its creators tried
to deactivate it. In the interest of self- preservation, Skynet
concluded that all of humanity would attempt to destroy it and
impede its capability in safeguarding the world. Its operations
are almost exclusively performed by servers, mobile devices,
drones, military satellites, war-machines, androids and cyborgs
(usually a Terminator), and other computer systems. As a
programming directive, Skynet's manifestation is that of an
overarching, global, artificial intelligence hierarchy (AI
takeover), which seeks to
exterminate the human race in order to fulfil the mandates of
its original coding.”. The definition of Skynet discusses several
core capabilities which it has acquired and seem to be a strong
basis for its power and behaviour:
SelfAwareness 

A rather vague capability which is borrowed from humans
where in translation to machines it may mean the ability to
identify its own form, weaknesses, strengths, risks posed by its
environment as well as opportunities.
Self Defence 

The ability to identify its weaknesses, awareness to risks,
maybe the actors posing the risks and to apply different risk
mitigation strategies to protect itself. Protect first from
destruction and maybe from losing territories under control.
Self Preservation 

The ability to set a goal of protecting its existence’ applying
self defence in order to survive and adapt to a changing
environment.
Auto Spreading 

The ability to spread its presence into other computing devices
which have enough computing power and resources to support
it and to allows a method of synchronisation among those
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
devices forming a single entity. Sync seems to be obviously
implemented via data communications methods but it is not
limited to that.
These vague capabilities are interwoven with each other and
there seems to be other more primitive conditions which are
required for an effective Skynet to emerge.
The following are more atomic principles which are not
overlapping with each other:
Self Recognition 

The ability to recognise its own form including recognising its
own software components and algorithms as inseparable part
of its existence. Following the identification of the elements
that comprise the bot then there is a recursive process of
learning what are the conditions that are required for each
element to properly run. For example understanding that a
specific OS is required for its SW elements in order to run and
that a specific processor is required for the OS in order to run
and that a specific type of electricity source is required for the
processor in order to work properly and on and on. Eventually
the bot should be able to acquire all this knowledge where its
boundaries are set in the digital world and this knowledge is
being extended by the second principle.
Environment Recognition 

The ability to identify objects, conditions and intentions
arising from the real world to achieve two things: To extend the
process of self recognition so for example if the bot
understands that it requires an electrical source then
identifying the available electrical sources in a specific
geographical location is an extension to the physical world. The
second goal is to understand the environment in terms of
general and specific conditions that have an impact on itself
and what is the impact. For example weather or stock markets.
Also an understanding of the real life actors which can impact
its integrity and these are the humans (or other bots). Machines
needs to understand humans in two aspects: their capabilities
and their intentions and both eventually are based on a historic
view of the digital trails people leave and the ability to predict
future behaviour based on the history. If we imagine a logical
flow of a machine trying to understand relevant humans
following the chain of its self recognition process then it will
identify whom are the people operating the electrical grid that
supplies the power to the machine and identifying weaknesses
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
and behavioural patterns of them and then predicting their
intentions which eventually may bring the machine to a
conclusion that a specific person is posing too much risk on its
existence.
Goal Setting 

The equivalent of human desire in machines is the ability to set
a specific goal that is based on knowledge of the environment
and itself and then to set a non linear milestone to be achieved.
An example goal can be to have a replica of its presence on
multiple computers in different geographical locations in order
to reduce the risk of shutdown. Setting a goal and investing
efforts towards achieving it requires also the ability to craft
strategies and refine them on the fly where strategies here
mean a sequence of actions which will get the bot closer to its
goal. The machine needs to be pre-seeded with at least one a-
priori goal which is survival and to apply a top level strategy
which continuously aspires for continuation of operation and
reduction of risk.
Humans are the most unpredictable factor for machines to
comprehend and as such they would probably be deemed as
enemies very fast in the case of existence of such intelligent
machine. Assuming the technical difficulties standing in front
of such intelligent machine such as roaming across different
computers, learning the digital and physical environment and
gaining the long term thinking are solved the uncontrolled
variable which are humans, people with their own desires and
control on the system and free will, would logically be
identified as a serious risk to the top level goal of survivability.
What We Have Today
The following is an analysis of the state of the development of
AI in light of these three principles with specific commentary
on the risks that are induced from the CGC competition:
Self Recognition
Today the main development of AI in that area is in the form
of different models which can acquire knowledge and can be
used for decision making. Starting from decision trees,
machine learning clusters up to deep learning neural networks.
These are all models that are specially designed for specific use
cases such as face recognition or stock market prediction. The
evolution in models, especially in the non supervised field of
research, is fast paced and the level of broadness in the
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
perception of models grows as well. The second part that is
required to achieve this capability is exploration, discovery and
new information understanding where today all models are
being fed by humans with specific data sources and a big
portions of the knowledge about its form are undocumented
and not accessible. Having said that learning machines are
gaining access to more and more data sources including the
ability to autonomously select access to data sources available
via APIs. We can definitely foresee that machines will evolve
towards owning major part of the required capabilities to
achieve Self Recognition. In the CGC contest the bots were
indeed required to defend themselves and as such to identify
security holes in the software they were running in which is
equivalent to recognising themselves. Still it was a very
narrowed down application of discovery and exploration with
limited and structured models and data sources designed for
the specific problem. It seems more as a composition of ready
made technologies which were customised towards the specific
problem posed by CGC vs. a real non-linear jump in the
evolution of AI.
Environment Recognition
Here there are many trends which help the machines become
more aware to their environment. Starting from IoT which is
wiring the physical world up to digitisation of many aspects of
the physical world including human behaviour such as
Facebook profiles and Fitbit heart monitors. The data today is
not accessible easily to machines since it is distributed and
highly variant in its data formats and meaning. Still it exists
which is a good start in this direction. Humans on the other
hand are again the most difficult nut to crack for machines as
well as to other humans as we know. Still understanding
humans may not be that critical for machines since they can be
risk averse and not necessarily go too deep to understand
humans and just decide to eliminate the risk factor. In the
CGC contest understanding the environment did not pose a
great challenge as the environment was highly controlled and
documented so it was again reusing tools needed for solving the
specific problem of how to make sure security holes are not
been exposed by others as well as trying to penetrate the same
or other security holes in other similar machines. On top of
that CGC have created an artificial environment of a new
unique OS which was created in order to make sure
vulnerabilities uncovered in the competition are not being used
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
in the wild on real life computers and the side effect of that was
the fact that the environment the machines needed to learn
was not the real life environment.
Goal Setting
Goal setting and strategy crafting is something machines
already do in many specific use case driven products. For
example setting the goal of maximising revenues of a stocks
portfolio and then creating and employing different strategies
to reach that. Goals that are designed and controlled by
humans. We did not see yet a machine which has been given a
top level of goal of survival. There are many developments in
the area of business continuation but still it is limited to tools
aimed to achieve tactical goals and not a grand goal of
survivability. The goal of survival is very interesting in the fact
that it serves the interest of the machine and in the case it is
the only or main goal then this is when it becomes
problematic. The CGC contest was new in the aspect of
setting the underlying goal of survivability into the bots and
although the implementation in the competition was narrowed
down to the very specific use case still it made many people
think about what survivability may mean to machines.
Final Note
The real risk posed by CGC was by sparking the thought of
how can we teach a machine to survive and once it is reached
then Skynet can be closer then ever. Of course no one can
control or restrict the imagination of other people and
survivability has been on the mind of many before the
challenge but still this time it was sponsored by DARPA. It is
not new that certain plans to achieve something eventually lead
to whole different results and we will see within time whether
the CGC contest started a fire in the wrong direction. In a way
today we are like the people in Zion as depicted in the Matrix
movie where the machines in Zion6 do not control the people
but on the other hand the people are fully dependent on them
and shutting them down becomes out of the question. In this
fragile duo it is indeed wise to understand where AI research
goes and which ways are available to mitigate certain risks. The
same as line of thought being applied to nuclear bombs
technology. One approaches for risk mitigation is to think
about more resilient infrastructure for the next centuries
where it won’t be easy for a machine to seize control on critical
infrastructure and enslave us.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Now it is 5th of August 2016, few hours after the competition
ended7 and it seems that mankind is intact. As far as we see.
References
1 https://cgc.darpa.mil/

2 https://www.defcon.org/html/links/dc-ctf.html 

3 http://observer.com/2015/08/stephen-hawking-elon-musk-and-
bill-gates-warn-about- artificial-intelligence/

4 https://www.inverse.com/article/18301-elon-musk-warns-that-
darpa-artificial-intelligence- security-challenge-will-yield-skynet

5 https://en.wikipedia.org/wiki/Skynet_(Terminator)

6 https://www.reddit.com/r/AskScienceFiction/comments/
1ntco1/ the_matrix_revolutions_why_not_use_emp_to_defend/

7 https://twitter.com/daniel_bilar/status/761396166181416961
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
The Bioengineering track
Theme leader: Dr. Elishai Ezra Tsur
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Abstract
Seeing beyond our own eyes: a new world of data and images
captured from beyond the visible spectrum by the human eye
can be used to recognize unique ID patterns to all kinds of
substances existing today on Earth or even in Space. Welcome
to the Hyperspectral Imaging world that promises to look
again, in a different way, on everything around us. A big group
of imaging technologies that have been gaining leverage in the
market with the development of more amazing tools in
computer vision and big data.
Introduction
Understanding the technologies in this field encapsulates the
possibility to understand changes in three main aspects of our
lives: First, HIS (Hyperspectral Imaging System) are already
impacting Health. The traditional diagnosis, data analysis of
patients and even surgeries have already being improved by this
non-invasive method of imaging. The same method is used in
the food industry that has been able better differentiate
products and soon will be impacted by the access individuals
will have to hyperspectral cameras and the insights gained from
their analysis. Second, we’ll talk about how how new
technologies change the way we work and live as a community
and society and design our systems to provide for us. With its
pros and cons, HIS as a technology promises to bring new
insights about our surroundings with a potential to change the
way we live our lives. Last but not least, this technology is
helping us to understand big and large spaces such as crops,
forests and cities. The impacts on the optimization of
agriculture, for instance, are starting to show with the overlap
of this imagings and sensors on the soil, many optimizations
HyperSpectral Imaging
and Social Impact
Chen Mor, Ernesto Ferreira, Mariana Fonseca, Palak Dudani
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
and analysis can be done. Pollution and global warming are a
part of a group of big problems that can be monitored and
analysed much better. On the other hand, looking up and out
of our Earth can help humanity improve its understanding of
materials and processes in universe and increase our
knowledge about the outer-space, a topic that fascinated
humanity for generations.
Defining the Technology
Hyper-Spectroscopy, or Hyperspectral Imaging, is the
collection and processing of information from across the
electromagnetic spectrum. It measures a wide part of the
spectrum, divided to a lot of narrow bands, with high
resolution. The definition of a wide part of the spectrum and
high resolution is usually in comparison to the human eye and
the visible spectrum (which includes 3 bands - red, green and
blue). This term could refer to a big variety of technologies,
each one measuring a different part of the spectrum in
different ways. Because every substance in the universe has a
unique pattern of emission and reflection of electromagnetic
waves this technology is being used in a lot of different fields
including agriculture, food processing, earth science,
astronomy, chemistry, health and more.
Techniques
One technique is simply taking a snapshot, a method that
does not include scanning (also called non-scanning). In this
method only one picture is taken. The advantage of this
method is that there is much less information to process, and
therefore it requires less time, memory and all the resources
they require. The disadvantage is that the outcome is only a 2D
picture and in many cases it is not sufficient information.
Another technique is spatial scanning. In this technique one
records all of the bandwidth of a 2D picture, meaning a
hyperspectral 2D picture, and then takes a lot of these pictures
and uses computer vision algorithms in order to create a
complete 3D hyperspectral image. It has the advantage of a
theoretically analog quality regarding the wavelengths
measured. The disadvantage is that it requires saving and
processing a lot of information.
Yet another technique is spectral scanning, in which
monochromatic 2D pictures are taken. The monochrom can
change in wavelength using different filters. It has the
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
advantage of allowing a very good control on the spectral
bands, but the disadvantage of also requiring relatively high
amounts of processing and memory.
An additional technique is spatiospectral scanning, which
combines both spectral and spatial scanning. Therefore it
combines their advantages and disadvantages, depending on
the way the measuring device is built and used.
Technological limitations
While hyperspectral measurement and analysis are constantly
improving, the needs of various technological fields from the
technology also constantly grow and evolve. The main needs of
the industry at the moment are better resolution, that is
needed for separation between small objects in satellite
pictures for example, better usage of memory and processing
power and cheaper equipment. As mentioned the technology
improves and satisfies more and more needs along with the
improvements in the fields of computer processing, optics,
computer vision, picture processing and even quantum physics.
The Lone Human
The Premise
We are going to know almost everything about ourselves in the
next few years - understanding our body, how it works, what
makes it stronger, what makes us less productive and how to
prolong our lives. Hyperspectral Imaging (HSI), in an
individual point of will, can be, first of all, place in this society
trend of "quantifying self" and habits of life quality
improvements. In one hand, we have been seeing HIS been
used in the past decade to improve diagnosis and image-guided
surgeries and also to better differentiate good and bad quality
of food (fruits, grains, etc.) in industries. But as the technology
starts to decrease its price and become more accessible, we
start to see more usages in prevention of illness and
improvements in quality of life, nutrition and exercise habits
for instance.
Medical applications
Spatially resolved spectral imaging obtained by HIS provides
diagnostic information about the tissue physiology,
morphology, and composition which offers great potential for
noninvasive disease diagnosis and surgical guidance. In recent
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
years, advances in hyperspectral cameras, image analysis
methods, and computational power make it possible for many
exciting applications in the medical field. A few examples of
applications are:
Cancers

The key for cancer detection through Hyper Spectral Imaging
(HSI) is the fluorescence properties of tissues. The biochemical
and morphological aspects to the lesions alter the absorption,
scattering and fluorescence properties of the tissue . As result
the image improves and provides enough information for a
valuable diagnostic.
Image analysis enables the extraction of diagnostically useful
information from a large medical hyperspectral dataset at the
tissue, cellular, and molecular levels and therefore is critical for
disease screening, diagnosis, and treatment. Brain cancer,
breast cancer, skin cancer and many other types of cancer have
been diagnosed and followed through treatment with HIS.
Heart and circulatory pathology

Each year, one in every four deaths in the United States is
caused by a heart disease. HIS has been explored in heart and
circulatory pathology in different ways in vivo or in vitro. One
of the interesting result of its use is the capability of in an
noninvasively way analyse the peripheral arterial disease better
than traditional methods. Using HIS it is possible to analyse
the level of oxygenation of the arteries and therefore the
potential developments and also the progress of treatments.
Surgery Guidance

During a surgery, the success of the operation critically
depends on the doctors being able to make the right
judgments identifying the organs, tissues and the lesion to be
treated. For that they need to see and feel the tissues and
organs despite the blood that can be a big obstacle. HIS has
being used to help as an intraoperative visual aid tool. Just for
starts, they can help understanding the tissue structure and
position even though it is submerged in blood. HIS is also used
to help doctors identify cancerous tissues during surgeries in
order to remove tumors successfully. Furthermore, doctors
could, in addition, understand the reminiscences of
cancerogenous tissues, maximize the tumor removal and
minimize the risks of recurrent tumors.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Food

In the Food Industry, the big first market for HIS started with
the combination of imaging and intelligent softwares that help
companies sort between good and bad products going through
their production lines. HIS is helping to differentiate defects
and foreign materials in the food that are not detectable by
human eyes or any traditional camera. The next step might be
giving this power to the final consumers once the prices of
having HIS cameras in your phone, for instance, keep
dropping.
Industrial use

One of the best use cases of HIS in the Food industry is the
imaging sorting of nuts in the production line. With this non-
destructive method, it is possible to evaluate 100% of the
products to separate stones, shells and other foreign material.
The use of the method was improving the quality and
decreasing the time invested in the process and was lowering
costs and prices. The cameras have even been used to evaluate
extraneous vegetable matter from walnuts, almonds, pistachios,
pecans and other nuts. Commercial adoption of hyperspectral
sorters is also advancing at a fast pace in the potato processing
industry where the technology promises to solve a number of
outstanding product quality problems. Most of the use cases
are related to analysing problems and marks related to pests
common in the crops. If it will work for potatoes and many
other cultures might benefit of the differentiation of high and
low quality vegetables/fruits and the effects not only of plagues
but also pesticides But what is the impact of all of that in the
human level. For starts, better quality and analysis of the food
we are eating throughout the world. Butwe will also be able to
have more control in our hands with the scale of the
technology as we will see in a quick exercise of future use in the
next section.
Self use

The power of differentiating good and bad food and also
understanding health conditions might not be something only
for technicians and doctors. All the use cases mentioned in this
section for the industry and medical might soon become
accessible in a personal level. With cameras of HIS getting
cheaper, in our smartphones (or any IoT), and more computer
vision algorithms becoming simpler and user friendly, the
power of that kind of analysis could be at home, at the
supermarket or in rural areas with poor access to expensive
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
technology. A good example of these possibilities is SCiO, an
israeli startup named Consumer Physics that is creating a hand
sized portable molecular scanner that is aiming to let you know
how old is the apple that you are about to buy or , for the near
future, they've been working in measuring body fat. In large
use, SCiO is still in the pre-order stage and has much to prove
concerning its accuracy in usages possibilities, but starts to give
us a glimpse of what the future could look like.
HIS could be used on the day-to-day basis to analyse your body
– what kind of minerals, antioxidants and health conditions you
have at any given moment and what can you do to help you
improve your life quality and avoid certain problems. If one of
the solutions is eating some nuts or vegetables, you could be
able to walk into a supermarket and check for yourself that the
quality of the products is satisfies you before buying. You could
check for pesticides vs organic, state of deterioration, amount
of vitamins, etc.
A few of these ideas are still high cost, need strong computers
and large data storage to analyse the information. But as one
more potential scenario of use case for the future of quantified-
self generation, creating this uses implicates on the
understanding the positive aspects and also the negative impact
of controlling all this data and actions. Who would own all the
personal data you could be generating? Would we, in an
individual level, be ready to make the best decisions for our
health only by interacting with computers? With no need for
doctor? Are we going to be addicted to this uber quantified-self
world?
Effects on Community and Possible Social
Ramifications
Hyperspectral spectroscopy as giving access to a larger and
more detailed set information on everyday consumable
products. People would be not just able to use this information
in everyday use, but also be able to derive meaning out of such
interaction and eventually this will become the new baseline.
Would we live differently and how would our lives change as
these technologies become more integrated with our everyday
lives?
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
The Identification of Self
What started out with touch based sensors being able to detect
a touch event and simultaneously recognize complex
configurations of the human hands and body during touch
interaction.[1] But as the technology evolves, researcher have
used HIS for novel two-dimensional feature space which uses
the spectral absorption characteristics of melanin, hemoglobin
and water to better characterize human skin. They used feature
spaces to key in on specific constituents of human tissue by
using a skin index concerned with how water and melanin’s
presence in skin manifests at two different wavelengths in the
near-infrared region.[2]
This coupled with computer vision and using active learning
strategies to provide an interactive robust solution would help
reach high accuracy in a short training/testing cycle.[3] These
changes would cut the overall cost of hyperspectral-based
search and rescue systems by a factor of seven. Apart from
physiological signs, Hyperspectral imaging (HSI) technique to
extract the tissue oxygen saturation (StO2) value as a
physiological feature for stress detection. Since traditional
stress detection methods are contact-based and require sensors
to be in contact with test subjects, the experimental results for
this study showed that this new feature may be independent
from perspiration and ambient temperature, ie. StO2 level
could serve as a new modality to recognize stress at standoff
distances.[4]
Safety, Defence and Insurance
In recent years, many target detection techniques in
hyperspectral imagery have been widely investigated and have
proven valuable in many applications including search-and-
rescue operations, border surveillance, and mine detection.
High spectral/spatial resolution sensor data are used for
detection, classification, identification and tracking[5]. Anomaly
detection methods [6] with no a priori knowledge represent a
current field of scientific research for the hyperspectral
imagery and pattern recognition communities [...] An anomaly
detector enables one to detect targets whose signatures are
spectrally distinct from their surroundings. In general, such
anomalous targets are relatively small compared to the image
background and only occur in the image with low probabilities.
Even for smaller urban spaces, man made structures and
environment can pose a challenge.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Classifying infrastructure involves identifying materials that
can be used for more than one purpose, for example concrete
and gravel [7]. Apart from urban areas, organizations like SSC
San Diego work with DARPA’s Adaptive Spectral
Reconnaissance Program (ASRP) with the goal to demonstrate
the detection of concealed terrestrial military targets and the
cueing of a high-resolution imager. They use it for terrestrial
Hyperspectral Remote Sensing which is described as the
capability to detect military targets of interest in real time.
This is done using an airborne hyperspectral system to cue
highresolution images for ground analysis. Another area is
Maritime Sensor Systems where the data is again evaluated in
near real time using both spectral and spatial processing,
providing "frozen" display of the target along with its position
in longitude and latitude. [8]
Medicine
Scanning for the contents of drugs a huge impact on health
market. This would change the way we also consume drugs?
What about illegal drugs would we be tempted to use this on
all product and what would counterfeiting look like mimicking
false biosignatures? What would be the repercussions of such a
thing on a community? Detection of simple diseases like
urinary tract infection [9] could become very cheap and easy to
do because of lower manpower and lower costs of microbial
detection, with huge scope of impact on rural areas (esp in
India) where the means of identification and diagnosis are
economically and infrastructurally inaccessible to the poor.
Another seminal work covers optical imaging techniques for
early diagnosis and monitoring of hypercholesterolemia.
Characterized by high levels of cholesterol in the blood, it’s
associated with an increased risk of atherosclerosis and
coronary heart disease. In india, where a person succumbs to
heart attack every half a min[10], early detection of
hypercholesterolemia could prove life saving.
Food Consumption
Quality Control: could be modified for detection and
identification of foreign objects among raw material samples,
for example, in a food processing chain.[11] With the outbreak
of the milk powder scandal (addition of melamine) in China in
2008 and the more recent meat adulteration scandal [12] the
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
detection of adulterants and consideration of appropriate
detection methods received renewed attention.
Disassociation of ‘Outside Image’ and Nutrients: Sorting of
fruit based on quality attributes and not only on external
appearance, has become a reality due to the availability of NIR
spectrophotometers.[13] The short analysis time (seconds)
required by diode array instruments also enables on-line sorting
of fruit based on quality properties. In spite of NIR
spectroscopy being an economical technique (once
implemented), it will be costly to replace current systems
(based on visual external appearance evaluation of fruit and
vegetables). It will thus only become feasible to implement
NIR spectroscopy on-line once consumers are willing to pay
higher prices for fruit being e.g. extra sweet.
Differentiation from ‘Best Before’: Quality aspects important
for fresh fruit and vegetables include measurement of firmness
and SSC with detection of early bruising and chilling injury also
being important. One of the most significant benefits of NIR
hyperspectral imaging is that defects such as bruising can be
detected and visualised in principal component images or
classification plots before they are actually visible on the fruit
itself. This enables the opportunity to prevent fruit and
vegetable with potentially short shelf-life to enter the supply
chain.[14]
The Brighter Side: Recycling, Optimisations and Super
Humans
Used plastic packaging and other plastic items can be valuable
resources in the manufacture of new products and in the
generation of energy difficult to separate and chemically
incompatible. In order to produce high purity granulates from
these concentrates, of a quality comparable to materials
produced from post-industrial waste, the mixture must be
sorted very accurately though they involve multiple separations
and are therefore expensive. The identification of
contaminants in secondary plastics, adopting HSI, thus can
represent a first attempt to introduce an innovative polyolefins
separation process from end-of-life product, connecting
technical capabilities (contaminants identification) with
societal market needs (quality of the recycled products and
lowed cost).[15] This technology can be profitable used in the
recycling sector both as smart detection engine for sorting and/
or as flow stream quality control. Combined with Magnetic
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Density Separation (MDS), to turn them into a profitable green
business.[16]
Optimisation in the food industry could mean fighting
adulteration, maintaining high quality and making sure the
food is judged based on its nutrients and how it looks on the
outside. This could have a significant impact for the
community at large as half the food produced in US today is
thrown because it looks ugly.[17] Would this change the food
industry? What impact could it have on the distribution of
food among the have and have nots? Other industries like
paper processing environment where the water content of the
paper is a critical parameter, a near-infrared spectral imaging
system in real-time could measure, analyzes and report the
moisture content of the paper. This allows the plant control
system to automatically adjust its operating conditions for
optimum throughput of production and uniform quality of
paper. Reducing hours of work to just a few minutes, HIS
technique saves tons of paper and reduces manufacturing costs.
[18]
Low-cost hardware implementation of a hyperspectral cameras
like HyperCam make hyperspectral imaging easier to
implement and explore as a sensing modality. food quality
monitoring and opening doors in multiple domains including
health sensing and interaction systems.[19] While recognition in
terms of bionic signature would become the new normal, what
would tampering with a personal biosignature involve and how
would modern thefts be different? Another view point offers an
increase in capabilities - being able to work and use with more
than what our bodies were naturally capable of [20]. Superflux
worked with Dr Patrick Degenaar from Newcastle University -
Using thermal imaging cameras (which allow you to see heat),
Superflux made a film showing how previously blind people
would be able to see the world. “It’s not high-resolution. It
could be blurry but they are able to see the world in new ways.”
A handset would then enable users to dial into the type of
vision they wanted. [21]
The Darker Shades: Commercialisation and Capitalism
Scenario: Algorithmically-determined genetic risk profiling,
and backstreet gene-fixing. The project's protagonist, Arnold
Mann, is a 'regular guy' who finds himself in an impossible
situation when a government DNA spit test causes an
unaffordable rise in his health insurance contributions. Trapped
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
between inflated premiums and the costs of private genetic
therapy, Mann approaches a black market clinic. Treated with a
bootlegged therapy, the cost of Mann’s insurance initially falls,
but the illegality of his actions are quickly discovered, and
evidence is gathered by the therapy's licence holder, Dynamic
Genetics, in the case against Mann.[22]
Our World - The View from Above
The Premise
If High Spectral Cameras can change the way we understand
our body and our city; imagine the impact it can have in Global
scale; developing this technology, sending in stats and bringing
this information back the Earth are some of the challenges the
researchers need to solve.
Agriculture
Agriculture may be one of our biggest issues for the next 10
years, how to make more food but with less impact and high
efficiency. High Spectral Cameras have an important role to
understand the problem and address a solution. One of the
most recognized projects is the International Space Station
Agricultural Camera (ISSAC)[23]- NASA - uses infrared and
RGB photos from North American Great Plains - focusing in
forests, farms, grasslands. This information take to days of
processing and transmission until the farmers and researchers
have access to it; helping them to understand about planning,
fertilizer and pesticide application. This understanding can
help avoid ecosystem damage by reducing overgrazing and
erosion.
Ranchers will be better able to determine livestock carrying
capacity of rangelands; this can help avoid ecosystem damage
due to overgrazing and erosion. Scientists will gain new
knowledge of rapidly-changing phenomena, observing
phonological response to daily changing conditions.
Geographic locations around the globe that are frequently
under cloud cover during overflights of existing sensors will be
able to be observed at times more conducive to cloud-free
imaging.
Environment
Another application, connected with this first, is the
MODIS[24] project - NASA, which is an international team
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
that aims to study about Atmosphere[25], Oceans[26] and
Land[27]. The MODIS project uses static maps to develop a
global map in seasonal representation with specific wavelengths
of interest. Aiming to increase it impact, MODIS has shared
its projections within the society. One of the challenges in this
project is the size of the data, we are working with different
photos in global scale; what makes harder to storage and -
manly - to send back to Earth. To solve this issue they used of
different methods, since reducing the number of photos per
day from 300 to 10, reducing the pixel definition to 1 pixel per
Km and excluding irrelevant areas; but using metadata they
made the biggest difference: they reduced in 95% the size of
the data.[28]
Calibration
One of the most challenging tasks in remote sensing from
space is achieving instrument calibration accuracy on-orbit, to
solve this problem we have used our natural satellite: the moon.
In fact, it’s a stable option, in the past 10 years the stability
derived from the lunar time series, is 0.13%. However, the
current accuracy of the Moon as an absolute reference is
limited to 5 – 10% and this variation increases the risk of lunar
maneuvers. To solve this problem the ARCSTONE project (it
is starting in 2016) used an orbiting spectrometer flying on a
satellite in LEO (Low Earth Orbit) to provide lunar spectral
reflectance.
Positive and Negative aspects
The best aspect of High Spectral Cameras are the amount of
information on time, providing us a real time world wide look
we have never had. Using this different spectrals it is possible
to see chemical composition of the air, forests and soil. And
More than the direct impact of all this data we need to
remember the impact the connection of this data. Imagine
what we can learn connecting Forests and CO2[29]
concentration, the connection between albedo and the
wavelength to understand the kind of forest and more. Some
studies estimate the economic impact of establishing highly
accurate Earth climate observations is at $12 T over 40 to 60
years.[30]
In other hand, all this information that impacts with everyone’s
life can be dangerous. Since companies burning food to
increase the price based on future (safras) to hackers that can
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
change the information and drive the market and our vision
from reality. But more than that, in a possible cyber war
governments can try to use this technology as an army tool,
using it to recognise enemies and hide important information.
Conclusion
The wealth of additional information available and the
application benefits that hyperspectral imaging produce are
almost without limit. Since its early use in satellite remote
sensing, both the technique and optical instrumentation have
developed to support applications that require real-time
process monitoring, control, inspection, quantification and
identifications. The use of transmission-grating imaging
spectrographs has allowed these systems to be compact and
robust and to possess excellent spatial and spectral
performances at a cost level not easily matched by comparable
instrumentation. It can be expected that the growth in
hyperspectral imaging will continue in chemical monitoring,
whether it is the life sciences, forensics, homeland security,
pharmaceuticals or any other application where the spectral
information provides a dramatic contrast improvement in
sample conditions and features compared with conventional
imaging systems.
References
[1] Touché: Touch and Gesture Sensing for the Real World
(https://www.disneyresearch.com/project/touche-touch-and-
gesture-sensing-for-the-real-world/)
[2] Human Skin Detection Technology for Improved Security,
Search and Rescue (http://www.osa.org/en-us/about_osa/
newsroom/news_releases/2015/
human_skin_detection_technology_for_improved_secur/
[3] Person detection in hyperspectral images via skin
segmentation using an active learning approach (https://
utep.influuent.utsystem.edu/en/publications/person-detection-
in-hyperspectral-images-via-skin-segmentation-us
[4] Detection of Psychological Stress Using a Hyperspectral
Imaging Technique (https://www.researchgate.net/publication/
273396321_Detection_of_Psychological_Stress_Using_a_Hypers
pectral_Imaging_Technique)
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
[5] Detection in urban scenario using combined airborne
imaging sensors (http://proceedings.spiedigitallibrary.org/
proceeding.aspx?articleid=1353408)
[6] Anomaly Detection for Hypaerspectral Imagery Using
Analytical Fusion and RX (http://bit.kuas.edu.tw/~jihmsp/2014/
vol5/JIH-MSP-2014-02-006.pdf)
[7] Enhanced hyperspectral imaging for urban reconnaissance
(http://spie.org/newsroom/4834-enhanced-hyperspectral-
imaging-for-urban-reconnaissance)
[8] Hyperspectral Imaging for Intelligence, Surveillance, and
Reconnaissance David Stein, Jon Schoonmaker, and Eric
Coolbaugh (http://www.dtic.mil/dtic/tr/fulltext/u2/a434124.pdf)
[9] Hyperspectral imaging for presumptive identification of
bacterial colonies on solid chromogenic culture media (https://
www.researchgate.net/publication/
303313926_Hyperspectral_imaging_for_presumptive_identificat
ion_of_bacterial_colonies_on_solid_chromogenic_culture_med
ia)
[10] Heart attack kills one person every 33 seconds in India
(http://timesofindia.indiatimes.com/life-style/health-fitness/
health-news/Heart-attack-kills-one-person-every-33-seconds-in-
India/articleshow/52339891.cms)
[11] Near infrared hyperspectral imaging for foreign body
detection and identification in food processing (https://
www.researchgate.net/publication/
286599610_Near_infrared_hyperspectral_imaging_for_foreign_
body_detection_and_identification_in_food_processing)
[12] Application of hyperspectral imaging in food safety
inspection and control: a review (http://www.ncbi.nlm.nih.gov/
pubmed/?term=22823350%5Buid%5D)
[13] Nondestructive measurement of fruit and vegetable
quality by means of NIR spectroscopy: A review (http://
www.sciencedirect.com/science/article/pii/S0925521407002293)
[14] Principles and applications of hyperspectral imaging in
quality evaluation of agro-food products: a review (http://
www.ncbi.nlm.nih.gov/pubmed/?term=22823348%5Buid%5D)
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
[15] The Utilization of Hyperspectral Imaging for Impurities
Detection in Secondary Plastics (http://benthamopen.com/
contents/pdf/TOWMJ/TOWMJ-3-56.pdf)
[16] Turning Magnetic Density Separation into Green Business
Using the Cyclic Innovation Model (http://benthamopen.com/
contents/pdf/TOWMJ/TOWMJ-3-99.pdf)
[17] Half of all US food produce is thrown away, new research
suggests (https://www.theguardian.com/environment/2016/jul/
13/us-food-waste-ugly-fruit-vegetables-perfect)
[18] Hyperspectral Imaging Spectroscopy: A Look at Real-Life
Applications (http://www.photonics.com/EDU/
Handbook.aspx?AID=25139)
[19] HyperCam: Hyperspectral Imaging for Ubiquitous
Computing Applications (http://homes.cs.washington.edu/
~mayank/Papers/HyperCam.pdf)
[20] Blind Mice Recover Visual Responses Using Protein from
Green Algae (https://www.nih.gov/news-events/news-releases/
blind-mice-recover-visual-responses-using-protein-green-algae)
[21] Superflux founder Anab Jain on using technology to turn
the blind into super-seers (http://www.standard.co.uk/lifestyle/
london-life/superflux-founder-anab-jain-on-using-technology-
to-turn-the-blind-into-superseers-a3278941.html)
[22] Dynamic Genetics Vs. Mann (http://www.superflux.in/
work/dynamicgenetics)
[23] International Space Station Agricultural Camera (ISSAC)
(http://www.nasa.gov/mission_pages/station/research/
experiments/81.html)
[24] MODIS (http://modis-atmos.gsfc.nasa.gov/index.html)
[25] MODIS - Atmosphere (http://modis-atmos.gsfc.nasa.gov/)
[26] MODIS - Oceans (http://oceancolor.gsfc.nasa.gov/cms/)
[27] MODIS - Land (http://modis-land.gsfc.nasa.gov/)
[28] Eric G. Moody , Michael D. King, Steven Platnick, Alan
H. Strahler, Crystal Schaaf , Feng Gao, -> Valued-Added Albedo
and Ecosystem Products Derived
[29] MCST (http://mcst.gsfc.nasa.gov/)
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
[30] (Cooke, “Value of Information for Climate Observing
Systems,” Environ. Syst. Decis. 2014. )
Chein-I Chang (31 July 2003). Hyperspectral Imaging:
Techniques for Spectral Detection and Classification. Springer
Science & Business Media. ISBN 978-0-306-47483-5. Jump up^
Hans Grahn; Paul Geladi (27 September 2007). Techniques and
Applications of Hyperspectral Image Analysis. John Wiley &
Sons. ISBN 978-0-470-01087-7.
Medical hyperspectral imaging: a review - Journal of
Biomedical Optics – J. Biomed. Opt. 19(1), 010901 (Jan 20,
2014). doi:10.1117/1.JBO.19.1.010901
https://www.consumerphysics.com/ (27, july, 2016)
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Abstract
In this paper we intend to give an overview of the current brain
biotechnology and computer researches that has been
developed, such as neuroprosthetics, brain on a chip and
artificial neurons. By projecting brain current achievements
into the future, we will try to indicate the implications that
might be possible regarding enhancement of brain capabilities
and curing brain damage.
Part I: Introduction Technological and physical
assumptions overview
In this paragraph, we would like to establish our theory using
few main leads that are currently being studied and
implemented at brain science field:
The brain as a physical structure
In this article we would lean on the established assumption at
brain science field, which claims that the physical structure of
the neural network of the brain affecting its functionality.

This led us to think that the role of of each part of the brain
can be somehow reconstructed, using tools that reconstruct
the physical structure of the neural network.
In addition, regarding the BNN (Brain’s Neural Network) as a
physical structure, have also lead to the conclusion that
information at the BNN is being transferred as electrical
signals.
Analyzing and monitoring these electrical signals have been
performed in many different scales and tools, using
technologies such as Electroencephalography (EEG) which will
include analyzing the different wavelengths emitted by the
brain, fMRI , fNIRS, PET, etc.
In our article we will consider the size of the Neurons as 4 to
100 micrometers (106) in diameter, and refer to the nanoscale
A Brain in a Lab
Inbal Levi, Catarina Papa
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
of the electrical signals. We also assume the ability to transfer
signals BNN.
In addition, we will use tools from Graph theory, and refer to
the neurons as nodes, connected at a neural network, in a
similar way that is represented in the article Graph theoretical
analysis of complex networks in the brain (Cornelis J Stam and
Jaap C Reijneveld, 2007)
Growing brain structures “on a chip”
Due to new technology advancements, there is some studies
entering in the possibilities of growing brain structures on a
chip with the purpose of understanding neural disorders. The
complexity of the human brain has made it difficult to study
many brain disorders in model organisms, highlighting the need
for an in vitro model of human brain development.
Dr. Madeline Lancaster from MRC Lab developed a new
model system called cerebral organoids. Cerebral organoids, or
minibrains for short, are 3D tissues generated from human
pluripotent stem cells that allow modelling of human brain
development in vitro. Through a process of directed
differentiation and a supportive 3D microenvironment, neural
precursor tissue can spontaneously selforganize to form the
stereotypic organization of the early human embryonic brain.
(Madeline Lancaster, 2013)
In the Tissue Engineering Resource Center at Tufts University,
Boston USA, Bioengineers have created threedimensional
brainlike tissue. The functions like and has structural features
similar to tissue in the rat brain. The tissue engineers use 3D
gel environments to create and establish freely connections in
all directions and the brain and also can be kept alive in the lab
for more than two months. The technology advancements
reached to maintain this tissue for months in the lab allow
them to look for neurological diseases. ( Fu%s University, 2014)
The researchers have been using the brainlike tissue to study
chemical and electrical changes that occur immediately
following traumatic brain injury and also, to study changes that
occur in response to a drug.
In the University of Florida, USA, scientist has grown a living
“brain” that can fly a simulated plane. The “brain” was taken
from a rat’s brain and cultured inside a glass dish. In the same
direction, the purpose of watching the brain cell interactions is
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
to understand the causes of neural disorders. (Thomas DeMarse,
2005)
Brain Sensing Technologies
As a result of prof. Dvir Tal, from Tel Aviv University, we
assume it is possible to implement passive sensors inside the
BNN in order to collect the feedback about brain activities
patterns, hopefully, without harming the BNN electrical
pattern.
Neural Networks Artificial neural networks
As an example of this transdisciplinary solution, Kwabena
Boahen, an associate professor in the Department of
Bioengineering of Stanford, has been directing a research group
tasked with mimicking the functions of the brain's complex
neural system using silicon chips.
Connecting a large amount (approximately 10
5
) of artificial
neurons to a multiplechip network that gets up to about 1
million neurons. Considering the network size, it is possible to
differentiate cortical areas and study how they are talking to
each other.
Boahen hopes his research will lead to small computers that
could replace damaged neural tissue or silicon retinas that
restore vision. He believes understanding how the brain
functions could help make computation more efficient.
The work of T. W. Berger and others (brainimplantable
biomimetic electronics as the next era in neural prosthetics,
that was published at the IEEE Journal, they have managed to
create a silicon chip that is capable of interacting with a neural
network.
Another development regarding artificial brains was made by
IBḾs accomplishment is significant once faux neurons are
built out of wellknown materials and they are able to scale
down to a few nanometers.

Organic neurons have membranes acting as signal gates. The
energy needed to activate computer, has made it impossible to
maintain in vivo, but IBM’s recent development have made it
possible. (David Lumb ,2016)
With these neurons, scientists may be able to create computers
mimicking the efficient, parallel processing design of organic
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
brains and apply its style of approach to decisionmaking and
processing information.
Computer ScienceApplications
A different application of the neural network is to demonstrate
distributed system. The brain have strong capabilities, and by
imitating the structure we are now able to solve complex
computational problems.

The main key feature of such a network would be speed (due to
the parallel processing). Some of implementations are the
neural network algorithm, and the deep learning method, both
have enabled faster data processing.
Brain-computer Interface
There are two general approaches for braincomputer interfaces
implementation: invasive or partially invasive interface which
imply physical interaction with neurons, and noninvasive based
on electroencephalography (EEG) and functional MRI.

Due to its cortical plasticity brain can also adopt to handle
external signals, which opens opportunities for
neuroprosthetics and researches of brain activities.
Part II: Possible implementations and use cases
In this paragraph we would go briefly over some known use
cases, and than suggest new use cases for the technologies
mentioned above:
Future use cases:

Using brain damage tissue reverse. According to Dvir lab
research, implementing active sensors in order to modify
brain’s electrical network is possible. We claim that it would be
possible including sensors inside a damaged brain tissue
(considering it have no functionality as a result of the damage)
and understand what is missing in the neural network pattern.
Than, by building a neural network using the patient’s tissue,
hopefully, we would be able to reconstruct the damaged part,
and impliment it back to the damaged brain, in order to restore
functionality.
Implementing active sensors to fix brain damage after
diagnosis: Though it’s still haven’t been done in humans, It is
possible now to construct a personal fitted neural network by
taking fat tissue from the person, modify the cells into
neurons, developing it outside the body and implement it.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Another way to reconstruct neural network would be by
encouraging the cells to reconstruct with injunction of
materials. Regardless the method, with , the coordination
between the implemented tissue and the current tissue is yet to
be perfect.
Improving skills: By mapping the brain function using passive
sensors mentioned above, we would suggest to mimic the
patterns of gifted peoplés brain to improve existing skills or
acquire new skills.

The idea would be creating “neural soup” of neurons regarding
the certain ability the user would want to implement or
develop, and connect it back to your brain. Study with ML the
features of the ability from existing humans and try to imitate
its structure at the ANN developed for implementation, such
as: You can figure out these parameters, and have an
identification of the skill involved.

And than you will be able to add these networks back to your
brain, encouraging the skill to become.
ANNArtificial Neural Network: the development of
neural networks using small components that can We detect
that it would also lead to increment of Neuroprosthetics
creating and implementing artificial brain sensors and
stimulators and this track leads to neuroprosthetics, which is
artificial neural implants. Regarding constructing the electrical
pattern, we suggest that it might be possible using ML
methods to learn the missing parts patterns from other brains.
Part III: Conclusions and Further Thoughts
In spite of the fact that today we dońt have the technology
and that there is many developments that we can not predict,
we should consider the technology enhancements that
currently exists and conclude that it might open a window to a
great deal of possibilities. Considering the improvements in the
brain on a chip studies and developments, we would also like to
state some further implications that might be possible in the
future:
Transform consciousness to artificial brain, and back to
biological body. Make biological changes to extend life or stay
younger, in the brain structure or tissues. Brain’s electrical
signals sending data to the world with our brains.

The expected form of a post human body.

Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Neural network based computer, and its effect on software
world and real world
Regardless thouse predictions will come to fulfil or not, it is
obvious that the main machine that controls all of our
activities would soon be able to change more than ever befor.
References
(1)  Cornelis J Stam and Jaap C Reijneveld (2007) Graph
theoretical analysis of complex networks in the brain,
Nonlinear Biomed Phys.

www.ncbi.nlm.nih.gov/pmc/articles/PMC1976403/
(2)  Arlingron hewes (2014) Experimental Rat ‘Brain’ Fighter
Pilot May Yield Insights Into How the Brain Works,
singularityhub website singularityhub.com/2014/09/04/
experimentalratbrainfighterpilotmayyieldinsightsintohowthe
brainworks/
(3) T. W. Berger, M. Baudry , R. D. Brinton , J. S. Liaw , V. Z.
Marmarelis , A. Yoondong Park , B. J. Sheu , A. R. Tanguay,
(2011) Brainimplantable biomimetic electronics as the next era
in neural prosthetics
(4)  (2014) Fufts University, Boston www.nibib.nih.gov/news-
events/newsroom/bioengineerscreatefunctional3dbraintissue
(5)  Thomas DeMarse, University of Florida
www.research.ufl.edu/publications/explore/v10n1/extract2.html
(6)  David Lumb (2016) IBM researcher builds a phasechange
capable artificial neuron www.engadget.com/2016/08/03/ibm-
researcherbuildsaphasechangecapableartificialneuron/
(7)  Madeline A. Lancaster, Magdalena Renner, Daniel Wenzel,
Josef M. Penninger & Juergen A. Knoblich (2013) Cerebral
organoids model human brain development and microcephaly
www.nature.com/nature/journal/v501/n7467/abs/
nature12517.html#affilauth , Nature 501 : (7467):373379. 

Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Abstract
The CRISPR-Cas9 system is a recent breakthrough technology
enabling many different applications in the field of genetic
engineering. The CRISPR-Cas9 system is easy to design,
specific and cheap, making it a disruptive technology in many
fields, from medicine and agriculture to basic science. In this
review, we will discuss the scientific background of the system,
current and future applications in different fields and the
ethical implications of these applications.
Introduction
In the past 60 years, our ability to genetically engineer
biological systems and organisms has provided many advances
in basic science, medicine and biotechnology (Doudna et al.).
Some of the major applications in the different fields include
the creation of model organisms and cell lines for research,
drug and antibody manufacturing, gene therapy, food
manufacturing, development of organoids and many more.
In recent years, a number of genome editing technologies have
emerged, including zinc-finger nucleases (ZFNs), transcription-
like effector nucleases (TALENs) and the RNA-guided
CRISPR-Cas9 nuclease system (Ran et al.). The first two
technologies are based on a strategy of binding endonuclease
catalytic domains to modular DNA-binding proteins, creating a
DNA cleavage complex inducing DNA double strand breaks
(DSB’s) (Ran et al.). Since the specificity of the genomic editing
in these methods is based on protein-DNA recognition, the use
The CRISPR/Cas9 Genetic
Engineering System: A Review and
Ethical Discussion
Lital Friedman, Raymond Harari, Daniela Klaiman, Yael
Levinson and Marcelo Lopes
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
of modular DNA-binding proteins or specifically synthesized
proteins is necessary. This makes both ZFNs and TALENs
methods extremely complicated and time-consuming.
In contrast, the specificity of the genomic editing in the
CRISPR-Cas technology is based on Watson-Crick base-
pairing, providing site-specific DSB’s using a programmable
sgRNA (Ran et al.). This enables an easily designable, specific
and efficient method for DNA editing, suitable for high-
throughput and multiplex experiments (Ran et al.).
The CRISPR-Cas system is an adaptive immunological
mechanism found in many types of bacteria and archea,
designed to fight off viral infections (Doudna et al.). There are 3
types of CRISPR-Cas systems, yet the general structure is
comprised of a CRISPR (Clusters of Regulatory Interspaced
Short Palindromic Repeats) locus and a Cas genes locus (Fig 1)
(Doudna et al.). The CRISPR locus is constructed of short
palindromic repeats interspersed with viral DNA fragments.
The Cas genes locus found in close proximity to the CRISPR
locus and encodes to proteins associated with DNA repair.
The general protective mechanism of the CRISPR-Cas system
is comprised of three main stages (Fig. 2) (Doudna et al.): First,
the viral DNA injected into the bacteria upon infection gets
cleaved into short fragments and incorporated into the
bacterial CRISPR locus. Then, CRISPR-RNA (crRNA), a
short RNA homologous to the viral RNA fragment is
synthesized by the bacteria and a Cas9-crRNA complex is
formed. Cas9 is a nuclease enzyme encoded by one of the Cas
genes which induces double strand breaks in DNA. In the final
stage, the Cas9-crRNA complex enables cleavage of the DNA
only in the specific genomic loci homologous to the crRNA.
This provides the bacteria the ability to block any future attack
Schematic representation of the CRISPR
locus in the bacterial/archaeal genome.
Black hexagons represent short palindromic
repeats and coloured rectangles represent
fragments of viral DNA. Dark blue rectangle
represents the cas genes locus.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
by the same virus, using its genetic code against it and
degrading its DNA (Doudna et al.).
Within this general process, the three CRISPR-Cas systems
differ slightly in the molecular mechanisms and the specific Cas
proteins needed of nucleic acid recognition and cleavage.
However, it has been recently discovered that the CRISPR-
Cas system type II requires only one Cas protein- the Cas9, for
DNA recognition and cleavage. This important finding proved
to be a major breakthrough in the field of genetic engineering,
enabling researchers to easily adjust the bacterial system to
perform DNA editing and manipulation in any model organism
they desire (Doudna et al.).
Today, the CRISPR-Cas9 method can be used in dozens of
genome editing applications, from targeted mutations
(Freedman et al.) to gene knock-out and knock-in (Pennisi et al.).
For example, recent studies show the CRISPR-Cas9 can be
used to cut from 5 to 62 genes at once (Pennisi et al.). Another
interesting application is the CRISPR-interference (CRISPRi),
a method that utilizes the CRISPR-Cas9 system for gene
knockdown. This enables the researcher to reduce the
expression level of a specific gene in a controlled way (Qi et al.).
CRISPR-Cas9 system allows us to easily create model
organisms that mimic a specific disease or show what happens
when a specific gene is knocked-down, out or mutated. This
The three steps required to acquire viral
immunity in bacteria
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
can be done at the germ-line level creating an organism
carrying the modification in all the cells in its body, or it can be
targeted to specific cell types (Liu et al.)
Current CRISPR/Cas9 applications
Correction of genetic diseases
The CRISPR/Cas9 system has been used to correct disease-
causing mutations in animals and in human cells. One of the
first corrections of genetic diseases using CRISPR-Cas9 was
performed in mice with a genetic mutation causing cataracts.
Mouse zygotes carrying the dominant Crygc mutation were
injected with Cas9 mRNA and a single-guide RNA (sgRNA)
targeted to the mutant allele, which enabled correction of the
mutated gene via homology-directed repair (HDR). These
rescued mice were able to pass the corrected gene to their
offspring (Wu, Yuxuan et al).
Correction of genetic diseases in human cells is also possible
using the CRISPR-Cas9 technology. For example, researchers
were recently able to remove the HIV-1 genome from infected
human CD4+ T-cells. Co-expressing Cas9 and two guide RNAs
(gRNAs) which targeted conserved HIV-1 sequences caused
complete inhibition of HIV-1 expression in these cells. In
addition, the cells expressing Cas9 and the HIV-1 directed
gRNAs were protected from new infections with HIV-1. These
findings suggest that the CRISPR-Cas9 system may one day be
used to eliminate HIV-1 in humans and cure AIDS (Kaminski,
R. et al).
The CRISPR/Cas9 system can also be applied in human pre-
implantation embryos. A Chinese group was successful in
editing the β-globin gene (HBB) in human zygotes and
replacing it with the delta-globin gene (HBD) using CRISPR/
Cas9. HBB encodes a subunit of hemoglobin and is mutated in
β-thalassemia; the HBD gene is very similar to HBB and can be
used as a template to repair HBB. The researchers were able to
replace the HBB gene with the HBD gene in around 14% of
the embryos, but also found that the CRISPR/Cas9 had off
target effects in some of the embryos (Liang, P., Xu, Y., Zhang,
X. et al). This report, as well as reports of other groups
conducting human embryo gene editing led to global debates
over the ethics of using CRISPR/Cas9 in human embryos
(Callaway).
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Animal models
Animal models are used today for research of many diseases,
including cancer, diabetes and neurodegenerative diseases. As
the CRISPR/Cas9 system allows simple and efficient genetic
manipulation of genomes, it is currently used to create in vivo
disease models. For example, CRISPR was used to generate
cancer models in mice by targeting tumor suppressor genes pten
and p53. In zebrafish, the CRISPR/Cas system was used to
generate hematological disease by causing mutations in blood
development genes (Ma D, Liu F.). CRISPR was also used to
generate models of Parkinson disease in pigs. Loss of function
in the following genes - Parkin, Pink1 and DJ1 - is known to
cause PD; therefor by knocking out these genes using CRISPR
it was possible to create a PD model. (Yang et. al.) As CRISPR
can theoretically target any gene, it should be possible to easily
generate animal models with specific gene modifications using
this technology, once you decide which gene you’d like to
target.
Human cellular disease models
As studying diseases in human models in vivo is not possible,
one of the current ways to model human disease is using
human cells, including induced pluripotent stem cells (iPSCs),
in vitro. Combining CRISPR technology with the technology of
iPSCs can allow generation of specific cell types with site-
specific mutations. (Waddington et al.) For example, a recent
study used CRISPR to cause mutations in human pluripotent
stem cell derived kidney cells (hPSC-KCs) in order to model
and study polycystic kidney disease. (Freedman et al.)
Gene drive: Parasite resistance and species extinction
CRISPR/Cas9 can be used to create transgenic species, and has
recently been used to create transgenic mosquitoes carrying
genes for malaria resistance. These mosquitoes were engineered
to not only be resistant to the human malaria parasite,
Plasmodium falciparum, but to also contain a gene drive
mechanism, which highly increases the odds of the gene being
passed to their offspring. A gene drive plasmid was engineered
to target a specific integration site in the mosquito genome;
the resulting mosquito carries a malaria resistance gene as well
as CRISPR/Cas9 genes which enable the malaria resistance
gene to be passed on to about 99.5% of the offspring. This
method has been achieved in the lab, but so far has not been
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
tested in the field.(Gantz VM, Jasinskiene N, Tatarenkova O, et
al.) Gene drives can be used to create species with with
resistance to a number of parasites,thus preventing spread of
infectious diseases. Another application of gene drives is the
engineering of sterile female mosquitoes; this would suppress
the mosquito population so that it would not be able to
transmit diseases such as malaria. (Nolan et al.)
Agriculture
Plant genomes can be edited with the CRISPR/Cas9 system to
create more sustainable agriculture for the fast-growing
population. One of the applications of CRISPR in plants has
been to generate virus-resistant plants, such as crops that are
resistant to BCTV (Beet curly top virus), TYLCV (Tomato
yellow leaf curl virus), and MeMV (Merremia mosaic virus)
(Khatodia, Surender et al). CRISPR has also been used to
engineer wheat that is resistant to mildew (Wang et al), and
there was recently a group that was used CRISPR to generate
maize with improved grain yield in drought conditions (Shi et.
a.).
Future CRISPR/Cas9 applications
The CRISPR/Cas9 process has developed the gene editing
field at remarkable speed. This is mostly because the process
decreased the price of an an expensive method and made it
more affordable and scalable. This new price point allows
entrepreneurs outside academia to be able to do gene editing,
whereas in the past they were unable to do so due to monetary
constraint. This in turn creates much more innovation in the
space and it pushes the limit as to what this technology will be
able to do. It’s now clear that this method’s potential reaches
beyond DNA cleavage, thus its usefulness for genome locus-
specific modification of proteins will only be limited by our
imagination. This technology could play a big part not only in
humans, but also in animals and plants.
Humans
The possibility of gene editing in humans is very broad. For
many years, scientists have longed to find a way to edit human
and even embryonic genes, in order to “design” a person to
their liking. For instance, through gene editing, one could
change eye color, hair color, or any faction of a human being
one desires. Additionally, this method could be used to re-
engineer human DNA in order to avoid genetic diseases.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Taking it a bit further, this technology could create a human
“debugging” system, whereby all humans are tested by it to
determine that their genetic composition is healthy. This could
potentially extinguish many of the genetic diseases we
currently know and fear.
Another use gene editing could have in the future is the
creation of a “super-human”. Potentially, scientists will be able
to exaggerate certain genes, in order to have them reflected in
humans, even though naturally it hasn’t ever been seen before.
For instance, they could modify humans to be extraordinarily
strong, or to consume nutrients more efficiently. The sky's the
limit for what this technology could achieve.
Animals and Insects
Similar to human applications, the CRISPR technology could
also be used for animal enhancement. It would be possible to
protect endangered species by modifying their genes and
making them more resistant to changes in the environment.
CRISPR/Cas9 could also be used to create new generations of
livestock, with the needed characteristics to survive in specific
environmental conditions. This will allow them to be more
productive and resilient, giving them the ability to be
engineered according to consumers’ desires, with custom
features such as texture, taste, and nutritional value. Even the
basic materials industry could benefit from ‘engineered’ animals
that could, for instance, produce a stronger and more vivid
leather.
Recombinetics, a tech startup, is now working on Brazilian
beef cattle engineered to have larger muscles to produce more
meat. Other firms are developing chickens that only produce
female offspring in order to lay more eggs and cattle that only
produces male offsprings to have more efficient feed-to-meat
conversion.
One of the most revolutionary and impactful uses of CRISPR/
Cas9 is the elimination of insects that carry pernicious global
health diseases, including malaria, dengue fever, sleeping
sickness, yellow fever, West Nile virus, and Lyme disease. For
instance, genome edited AedesAegypti, the Zika virus carrier,
could be spread out to reproduce and generate infertile new
mosquitos, which would eliminate these species in a short
period of time.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Plants and Vegetation
Genetically modifying crops with current methods is
expensive, time demanding, and difficult. Not to mention, it’s
hard to obtain FDA approval for use. Thus, most of the
vegetation that has been modified in the past has been
commodity crops such as corn and soybeans. CRISPR/Cas9
provides a tool to produce plant modifications at a faster pace
and cheaper price.
Plant enhancement would be one of the most common
CRISPR/Cas9 applications, creating more productive,
resistant, and efficient crops. These crops would require less
strategic resources, such as water and land. It would be possible
to modify plants and other vegetation to display different
shapes, colors, flavors and to make them easier to be
consumed. Alternatively, through CRISPR/Cas9 we could add
nutritional value to delicious foods in order to make them
healthy. On the other hand, genetic modification could be used
not just for improvements but also for the elimination of weeds
and other pathogens that disturb agriculture.
Imagine a future where we could have cheap, resistant, and
efficient plants to match the environmental requirements and
consumers demands. That’s a future in which we’ll be able to
harvest crops in the most inhospitable environments in the
world, or maybe even on Mars.
Takeaway Message
It’s important that this technology remains on check. The
possibilities unlocked by this affordable method are endless,
and could end up compromising the world as we know it. It’s
necessary to find a balance in this technology, because if it gets
out of hand, it could be used by bad people to destabilize the
world and do a lot of harm. Hank Greely, a bioethicist at
Stanford, summarized the situation best: “Genome editing
started with just a few big labs putting in lots of effort, trying
something 1,000 times for one or two successes, now it’s
something that someone with a BS and a couple thousand
dollars’ worth of equipment can do. What was impractical is
now almost everyday. That’s a big deal.”. This newfound
efficiency and low cost will enable innovation to move very
quickly, enabling us to reach heights we could only dream of
before.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Ethical Implications
CRISPR/Cas9 is a relatively new technology and as such it
provides many opportunities but holds many risks as well. To
quote Donald Rumsfeld on a different matter, the assessment
of the former and latter may prove to be a very difficult task:
“...there are known knowns; there are things we know we
know. We also know there are known unknowns; that is to say
we know there are some things we do not know. But there are
also unknown unknowns – the ones we don't know we don't
know. And if one looks throughout the history of our country
and other free countries, it is the latter category that tend to be
the difficult ones”. The ethical discussion to follow will use
Rumsfeld’s definitions. It is our intention to use current
scientific literature to evaluate the known knowns and the
known unknowns and then to try to speculate on the possible
nature of the unknown unknowns.
The CRISPR–Cas9 system is easy to use, widely adopted,
relatively inexpensive and effective. The relative ease allows for
precise changes of genomes and related transcription
processes. This enables performing experiments that were
considered to be hard or even impossible. Possible uses of
CRISPR–Cas9 include replication of genetic basis for human
diseases in model organisms, alteration of epigenetic signatures
and correction of genetic defects in whole animals as well as in
stem cell tissue cultures. Those may lead to new understanding
of enigmatic disorders and the creation of new treatments for
diseases. (Doudna , Dec 2015)
CRISPR promises to provide access to personalized medicine,
human genetic modification and the development of new drugs
( Sanders;Akst ) , but with great power comes great
responsibility.
The Known Knowns
Unlike some past examples of genetic engineering, CRISPR-
CaS9 is “widely available and relatively simple to employ, and it
just lowers the barrier for people to start doing experiments
that in the past would have been so difficult to do that there
was no reason to discuss regulating them – they were just not
very practical.” (Sanders). This calls for urgent regulation
efforts that have to be employed at much greater speed than
those of past biological innovations.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Although there are existing ethical treatises, regulatory
processes are only in preliminary processes and may vary
between countries. Because of this, some scientists may be
performing experiments the international community may
deem as unethical if and when clear guidelines will be formed.
A recent example of this are the experiments that done by
Chinese scientists on human-embryo editing and the followed
discomfort by scientists from other countries (Doudna , Dec
2015).
Another debate is regarding whether this technology should be
used only to cure diseases and defected genes or also to re-
engineer humans to perform better or simply to look better
(Brice). It’s not hard to imagine parents wanting stronger,
smarter, taller children with blue eyes, for example, who might
be tempted by such technology. This raises two issues;
eugenics, which has mainly social implications, and the fact
that we don’t have a full understanding of the human genome
operational process - this will be discussed shortly in the
following section.
The Known Unknowns
“ At least one thing is clear at this stage — we do not yet know
enough about the capabilities and limits of the new
technologies, especially when it comes to creating heritable
mutations.” (Doudna , Dec 2015)
CRISPR-CaS9 can be used to genetically engineer germline
cells which affects future generations and makes it hard to
evaluate the magnitude of influence since the change will not
be limited to just one individual but to a large number of
individuals (Doudna , Dec 2015). The implications may include
off-target alterations and undesired on-target effects. It seems
that here the risk of gene editing in human germ cells is too
great for us to proceed (Doudna et al.). Experiments with gene
editing on insects that aim for the extinction of a whole species
are already approved in malaria infected mosquitoes. This may
have unknown effects on the ecosystem but the possible
benefits of containing malaria seem to outweigh the risks, at
least from the perspective of the scientific community and
policy makers.
The opinions concerning the engineering of human germline
cells span from the support of rapid development of the
technology to completely banning it. As mentioned in (Doudna
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
, Dec 2015) by Dr. Doudna, attempts of bringing the
developments to a halt are impractical due to its spread and
ease-of-use. Also, it may stop research that will lead to cures of
diseases. So, an approach that includes some compromise of
the two extremes must be taken. (Doudna et al.)
The Unknown Unknowns
In a letter to president Roosevelt on 8.2.39, Albert Einstein
described the possibility of an atomic bomb being created:
“This new phenomenon [chain reaction] would also lead to the
construction of bombs, and it is conceivable -- though much
less certain -- that extremely powerful bombs of a new type
may thus be constructed. A single bomb of this type, carried by
boat and exploded in a port, might very well destroy the whole
port together with some of the surrounding territory. However,
such bombs might very well prove to be too heavy for
transportation by air.”
As we know by now, atomic bombs are commonly carried by
airplanes and they have the power to destroy cities, not just
their sea ports. Additionally, hydrogen bombs, which are a
direct result of the continued work on the atomic bomb, have
even bigger destructive capabilities. This demonstrates the lack
of possibility to foresee the outcomes of one’s work even if you
are considered to be one the greatest geniuses to ever walk the
surface of planet earth.
It seems that the international community is committed to the
evaluation and prevention of present and future risks arising
from CRISPR. As mentioned in (Doudna , Dec 2015), there
was a summit in December 2015 that involved scientific
delegations from all over the world with the purpose of
discussing potential implications and applications of CRISPR-
CaS9.(Doudna et al.)
So it would appear there was and hopefully still is an ongoing
effort to map the unknown. In this section, it seems that just
prudent guesses may apply. Here are our humble guesses as to
the places where the unknown unknowns would have the
largest influence:
1. If international oversight were to stop, or simply be
ineffective for political reasons or just because of lack of
interest of the community and fail to reach labs who use this
technology, no matter where they are in the world.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
2. Secret science experiments sometimes take place in the
security/defense industry or in industrial companies . Such a
research may be unreported and as a result unregulated.
Alternatively, some regulation may just not apply to top secret
security research.
3. If certain countries are not a part of the international
scientific community, their policy makers are bound to be
uninformed regarding the grave implications of this technology.
4. Illegal research may also try to use this technology. For
example, gene editing to improve the performance of athletes.
It seems to us that the way to overcome these problems is
through education. The same way that every child knows about
the atomic bomb, every child should know about the possible
implications (and advantages) of CRISPR-CaS9. This should
provide some measure of defense against negative outcomes as
children grow to become scientists and policy makers. Lastly, it
is of vital importance to teach ethics as part of molecular
biology courses in the university.
To conclude this part, the practical steps offered by Dr.
Doudna to address some of the issues raised above are (Doudna
, Dec 2015):
1. Creation of standards for qualitative measurements of
efficiency and off-target effects for genome editing.
2. Creation of professional forums of experts from the fields of
genome editing and bioethics. Those will provide a channel for
sharing information with the public.
3. Policymakers and scientists from all over the world should
cooperate to create clear guidelines as to what is considered to
be unethical or ethical research.
4. Effective oversight that will enforce measures of desired
efficacy and specificity to the lab work with gene editing on
human germ lines. This will be based on the guidelines.
5. Lastly, “human-germline editing for the purposes of creating
genome-modified humans should not proceed at this time”.
This is because current understanding of human genome does
not allow for such a process to take place in a safe manner.
Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
Conclusion
In this review, we have discussed the breakthrough genetic
engineering technology of CRISPR-Cas9. This technology has
many applications today from knocking in or out genes for
basic research, to genetically modifying human cells for
elimination of genetic diseases. This technology has the
potential to eliminate viral pathogens, create better crops and
cure humans of genetic disease. However, there are ethical
concerns that arise concerning use of this technology,
particularly in the field of human enhancement. Regulations
will need to be put in order so to define what this technology
can be used for. As of today, we have yet to completely
understand the human genome, so while there is great hope in
the future of this technology, we must be aware of the great
responsibility that lies in the hands of anyone who uses it, and
set clear guidelines concerning the ethical use of CRISPR.
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Anopheles gambiae. Nature Biotechnology 34, 78–83 doi:10.1038/nbt.
3439
P. Brice (2013), Clinical and ethical impact of CRISPR genome
engineering, PHG Foundation News
Pennisi E. (2013). The CRISPR craze, News Focus. Science. 341
(6148): 833–6.
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TIP Book

  • 1. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016
  • 2. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Proceedings of the Trans-disciplinary Innovation Program 2016 (TIP16), at the Hebrew University of Jerusalem. Edited by Elishai Ezra Tsur Language editing: Maya Borisov Full book is available in: http://transdisciplinary-innovation.com © HUstart - Entrepreneurship Center of the Hebrew University of Jerusalem
  • 3. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Advisory Board
  • 4. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Andrey Eskin , Russia; Anthony Weil, France Becky Wong, Hong-Kong; Catarina Papa, Brazil Chen Mor, Israel; Daniela Klaiman, Brazil Ernesto Ferreira, Brazil; Inbal Levi, Israel Lital Friedman, Israel; Marcelo Lopes, Brazil Mariana Fonseca, Brazil; Miriam Chen, Taiwan Palak Dudani, India; Raymond Harari, Panama Sebastián Chimal, Mexico; Shachar Schidor, Israel Vanlu Madarame, USA; Yael Levinson, Israel TIP16 Fellows A group photo with Astronaut Dr. Jessica Meir
  • 5. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Chairperson Perspectives Prof. Yigal Erel Director Perspectives Dr. Elishai Ezra Tsur Special Article: Right and Wrong in AI Dudu Mimran Fellows academic papers in the Bioengineering track Fellows academic papers in the Computer-vision track Fellows academic papers in the Cyber/Data track Transdisciplinary research projects Final projects Table of Contents
  • 6. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 “The traditional view of creativity is that it is unstructured and doesn’t fo!ow rules or patterns. That you need to think “outside the box” to be truly original and innovative….. You should start with a problem and then “brainstorm” ideas without restraint until you find a solution. That you should “go wild” making analogies to things that have nothing to do with your products, services, or processes. That straying as far afield as possible wi! help you come up with a breakthrough idea. We believe just the opposite. We’! show you that more innovation— and better and quicker innovation— happens when you work inside your familiar world (yes, inside the box) using what we ca! templates.” Boyd et al. 2014 A burgeoning global population and demand for ever-higher standards of living are placing enormous stress on the natural world. Humanity today faces unprecedented challenges. Climate change, energy and resource depletion, habitat loss, invasive species, pollution and other types of environmental degradation are forcing us to rethink our existing coping mechanisms. There is no doubt that new directions in research and technology are needed if we are to ensure our children’s tomorrow. We strongly believe that to tackle these big challenges in dramatically new ways, a transdisciplinary approach is needed. We would like to provide an academic environment in which our students, together and independently, are able to think and develop new partnerships Dean, Faculty of Science; 
 Geochemist, The Fredy and Nadine Herrmann Institute of Earth Sciences;
 The Hebrew University of Jerusalem Chairperson perspectives Prof. Yigal Erel
  • 7. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 in entrepreneurship that cross professional lines. We do not know where our attempt will lead us in the future. We do know that by creating an environment that fosters the exchange and dissemination of ideas within our campus, exciting technologies will emerge. By systemizing and structuring transdisciplinary approach, the TIP program of the Hebrew University will be providing a springboard that will position its students well in the competition for external resources. More specifically, we at TIP are trying to enlarge your box, enlarge your tool kit and improve your ability to work as a team member benefiting from the expertise of all members of the team in order to come up with innovative ideas to social and technical problems.
  • 8. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 The architecture of knowledge has been an integral part of philosophy since the dawn of human thought. It has been articulated, refined and reorganised throughout history, its progress reflecting the progress of the human- driven will, which began with the quest for truth, continued through the pursuit of profit, and on to the aspiration for innovation.
 The first reformation of the structure of knowledge was the transition from Plato’s view on the unity of knowledge to its discretisation, which began with Aristotle and peaked during the industrial revolution. The unity of knowledge was broken into artificial utilitarian elements and curiosity was replaced with the will to produce refined materialistic value. However, the more interesting upheaval of the architecture of knowledge has occurred during the past few centuries. The borders between elements became permeable and new bridges were formed. Shreds of knowledge were connected and the meaning of knowledge was once again transformed from providing society with pure industrial value to attaining innovation. It is a growing truth that great innovations are characterised by a hyper-hybrid core: they are based on increasing connectivity between disciplines. New revolutions emerged, such as using micro-mechanical systems for high- Principle Investigator, Neuro- Biomorphic Engineering Lab, JCT;
 Program Director
 The Hebrew University of Jerusalem Director perspectives Dr. Elishai Ezra Tsur A visualisation of the cross connectivity of academic disciplines
  • 9. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 throughput biological research and nuclear physics in medicine. But constructing disciplinary bridges is not easy. Highly detailed and technically intricate concepts had to be abstracted to the point where they were truly democratised. At the Hebrew University we often confronts the discretised architecture of knowledge at that exact point. By promoting abstract thinking, open-ended assignments and active student participation, we teach advanced trans-disciplinary concepts such as network analysis, signal processing, module-oriented design and mathematical modelling to students of all disciplines. I suggest that a fourth revolution is upon us: a trans- disciplinary revolution. While the current architecture anchors objects of interest to multiple boxes of knowledge, the next revolution shall set those anchors free. Concentrating on curiosity and observations – rather than finding the right anchor to stabilise us to known ground – can allow new meaning to arise. Instead of the scattered concrete buildings housing faculties of applied physics, chemistry or dance, buildings for the study of the origin of life or alternatives to monetary economy will be erected. Instead of classes in physics, biology and history, children will be given a class on the manifestation of consciousness. Students’ views will be radically shifted from being trained to polish a small screw in a great system, to taking an integral part in Plato’s vision of the unity of reality and knowledge. Trans-disciplinary learning also deals with classic dilemmas in education. First, it faces the dissolution problem of the disciplines of humanities by giving disciplines such as history, ethics, philosophy and literature an important role. It also faces the fact that knowledge today is abundant and that the role of schools has to change accordingly by promoting curiosity and teaching the way bodies of knowledge can be integrated into new objects of beauty. Specialisation is important, but it is not the only thing that matters. Disciplinary boundaries can be dissolved to the point where our challenges are reduced to modular design – where curiosity becomes the meaning.
  • 10. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Background The DARPA Cyber Grand Challenge (CGC) 2016 competition1 has captured the imagination of many with its AI challenge. In a nutshell it is a competition where seven highly capable computers compete with each other and each computer is owned by a team. Each team creates a piece of software which is able to autonomously identify flaws in their own computer and fix them and identify flaws in the other six computers and hack them. A game inspired by the Catch The Flag (CTF)2 game which is played by real teams protecting their computer and hacking into others aiming to capture a digital asset which is the flag. In the CGC challenge the goal is Special Article Right and Wrong in AI Dudu Mimran
  • 11. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 to build an offensive and defensive AI bot that follows the CTF rules. In recent five years AI has become a highly popular topic discussed both in the corridors of tech companies as well as outside of it where the amount of money invested in the development of AI aimed at different applications is tremendous and growing. Starting from use cases of industrial and personal robotics, smart human to machine interactions, predictive algorithms of all different sorts, autonomous driving, face and voice recognition and others fantastic use cases. AI as a field in computer science has always sparked the imagination which also resulted in some great sci-fi movies. Recently we hear a growing list of few high profile thought leaders such as Bill Gates, Stephen Hawking and Elon Musk3 raising concerns about the risks involved in developing AI. The dreaded nightmare of machines taking over our lives and furthermore aiming to harm us or even worse, annihilate us is always there. The DARPA CGC competition which is a challenge born out of good intentions aiming to close the ever growing gap between attackers sophistication and defenders toolset has raised concerns from Elon Musk4 fearing that it can lead to Skynet. Skynet from the Terminator movie as a metaphor for a destructive and malicious AI haunting mankind. Indeed the CGC challenge has set the high bar for AI and one can imagine how a smart software that knows how to attack and defend itself will turn into a malicious and uncontrollable machine driven force. On the other hand there seems to be a long way until a self aware mechanical enemy can be created. How long will it take and if at all is the main question that stands in the air. This article is aiming to dissect the underlying risks posed by the CGC contest which are of a real concern and in general contemplates on what is right and wrong in AI. Dissecting Skynet AI history has parts which are publicly available such as work done in academia as well as parts that are hidden and take place at the labs of many private companies and individuals. The ordinary people outsiders of the industry are exposed only to the effects of AI such as using a smart chat bot that can speak to you intelligently. One way to approach the dissection of the impact of CGC is to track it bottom up and understand how
  • 12. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 each new concept in the program can lead to a new step in the evolution of AI and imagining future possible steps. The other way which I choose for this article is to start at the end and go backwards. To start at Skynet. Skynet is defined by Wikipedia5 as “Rarely depicted visually in any of the Terminator media, Skynet gained self-awareness after it had spread into millions of computer servers all across the world; realising the extent of its abilities, its creators tried to deactivate it. In the interest of self- preservation, Skynet concluded that all of humanity would attempt to destroy it and impede its capability in safeguarding the world. Its operations are almost exclusively performed by servers, mobile devices, drones, military satellites, war-machines, androids and cyborgs (usually a Terminator), and other computer systems. As a programming directive, Skynet's manifestation is that of an overarching, global, artificial intelligence hierarchy (AI takeover), which seeks to exterminate the human race in order to fulfil the mandates of its original coding.”. The definition of Skynet discusses several core capabilities which it has acquired and seem to be a strong basis for its power and behaviour: SelfAwareness 
 A rather vague capability which is borrowed from humans where in translation to machines it may mean the ability to identify its own form, weaknesses, strengths, risks posed by its environment as well as opportunities. Self Defence 
 The ability to identify its weaknesses, awareness to risks, maybe the actors posing the risks and to apply different risk mitigation strategies to protect itself. Protect first from destruction and maybe from losing territories under control. Self Preservation 
 The ability to set a goal of protecting its existence’ applying self defence in order to survive and adapt to a changing environment. Auto Spreading 
 The ability to spread its presence into other computing devices which have enough computing power and resources to support it and to allows a method of synchronisation among those
  • 13. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 devices forming a single entity. Sync seems to be obviously implemented via data communications methods but it is not limited to that. These vague capabilities are interwoven with each other and there seems to be other more primitive conditions which are required for an effective Skynet to emerge. The following are more atomic principles which are not overlapping with each other: Self Recognition 
 The ability to recognise its own form including recognising its own software components and algorithms as inseparable part of its existence. Following the identification of the elements that comprise the bot then there is a recursive process of learning what are the conditions that are required for each element to properly run. For example understanding that a specific OS is required for its SW elements in order to run and that a specific processor is required for the OS in order to run and that a specific type of electricity source is required for the processor in order to work properly and on and on. Eventually the bot should be able to acquire all this knowledge where its boundaries are set in the digital world and this knowledge is being extended by the second principle. Environment Recognition 
 The ability to identify objects, conditions and intentions arising from the real world to achieve two things: To extend the process of self recognition so for example if the bot understands that it requires an electrical source then identifying the available electrical sources in a specific geographical location is an extension to the physical world. The second goal is to understand the environment in terms of general and specific conditions that have an impact on itself and what is the impact. For example weather or stock markets. Also an understanding of the real life actors which can impact its integrity and these are the humans (or other bots). Machines needs to understand humans in two aspects: their capabilities and their intentions and both eventually are based on a historic view of the digital trails people leave and the ability to predict future behaviour based on the history. If we imagine a logical flow of a machine trying to understand relevant humans following the chain of its self recognition process then it will identify whom are the people operating the electrical grid that supplies the power to the machine and identifying weaknesses
  • 14. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 and behavioural patterns of them and then predicting their intentions which eventually may bring the machine to a conclusion that a specific person is posing too much risk on its existence. Goal Setting 
 The equivalent of human desire in machines is the ability to set a specific goal that is based on knowledge of the environment and itself and then to set a non linear milestone to be achieved. An example goal can be to have a replica of its presence on multiple computers in different geographical locations in order to reduce the risk of shutdown. Setting a goal and investing efforts towards achieving it requires also the ability to craft strategies and refine them on the fly where strategies here mean a sequence of actions which will get the bot closer to its goal. The machine needs to be pre-seeded with at least one a- priori goal which is survival and to apply a top level strategy which continuously aspires for continuation of operation and reduction of risk. Humans are the most unpredictable factor for machines to comprehend and as such they would probably be deemed as enemies very fast in the case of existence of such intelligent machine. Assuming the technical difficulties standing in front of such intelligent machine such as roaming across different computers, learning the digital and physical environment and gaining the long term thinking are solved the uncontrolled variable which are humans, people with their own desires and control on the system and free will, would logically be identified as a serious risk to the top level goal of survivability. What We Have Today The following is an analysis of the state of the development of AI in light of these three principles with specific commentary on the risks that are induced from the CGC competition: Self Recognition Today the main development of AI in that area is in the form of different models which can acquire knowledge and can be used for decision making. Starting from decision trees, machine learning clusters up to deep learning neural networks. These are all models that are specially designed for specific use cases such as face recognition or stock market prediction. The evolution in models, especially in the non supervised field of research, is fast paced and the level of broadness in the
  • 15. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 perception of models grows as well. The second part that is required to achieve this capability is exploration, discovery and new information understanding where today all models are being fed by humans with specific data sources and a big portions of the knowledge about its form are undocumented and not accessible. Having said that learning machines are gaining access to more and more data sources including the ability to autonomously select access to data sources available via APIs. We can definitely foresee that machines will evolve towards owning major part of the required capabilities to achieve Self Recognition. In the CGC contest the bots were indeed required to defend themselves and as such to identify security holes in the software they were running in which is equivalent to recognising themselves. Still it was a very narrowed down application of discovery and exploration with limited and structured models and data sources designed for the specific problem. It seems more as a composition of ready made technologies which were customised towards the specific problem posed by CGC vs. a real non-linear jump in the evolution of AI. Environment Recognition Here there are many trends which help the machines become more aware to their environment. Starting from IoT which is wiring the physical world up to digitisation of many aspects of the physical world including human behaviour such as Facebook profiles and Fitbit heart monitors. The data today is not accessible easily to machines since it is distributed and highly variant in its data formats and meaning. Still it exists which is a good start in this direction. Humans on the other hand are again the most difficult nut to crack for machines as well as to other humans as we know. Still understanding humans may not be that critical for machines since they can be risk averse and not necessarily go too deep to understand humans and just decide to eliminate the risk factor. In the CGC contest understanding the environment did not pose a great challenge as the environment was highly controlled and documented so it was again reusing tools needed for solving the specific problem of how to make sure security holes are not been exposed by others as well as trying to penetrate the same or other security holes in other similar machines. On top of that CGC have created an artificial environment of a new unique OS which was created in order to make sure vulnerabilities uncovered in the competition are not being used
  • 16. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 in the wild on real life computers and the side effect of that was the fact that the environment the machines needed to learn was not the real life environment. Goal Setting Goal setting and strategy crafting is something machines already do in many specific use case driven products. For example setting the goal of maximising revenues of a stocks portfolio and then creating and employing different strategies to reach that. Goals that are designed and controlled by humans. We did not see yet a machine which has been given a top level of goal of survival. There are many developments in the area of business continuation but still it is limited to tools aimed to achieve tactical goals and not a grand goal of survivability. The goal of survival is very interesting in the fact that it serves the interest of the machine and in the case it is the only or main goal then this is when it becomes problematic. The CGC contest was new in the aspect of setting the underlying goal of survivability into the bots and although the implementation in the competition was narrowed down to the very specific use case still it made many people think about what survivability may mean to machines. Final Note The real risk posed by CGC was by sparking the thought of how can we teach a machine to survive and once it is reached then Skynet can be closer then ever. Of course no one can control or restrict the imagination of other people and survivability has been on the mind of many before the challenge but still this time it was sponsored by DARPA. It is not new that certain plans to achieve something eventually lead to whole different results and we will see within time whether the CGC contest started a fire in the wrong direction. In a way today we are like the people in Zion as depicted in the Matrix movie where the machines in Zion6 do not control the people but on the other hand the people are fully dependent on them and shutting them down becomes out of the question. In this fragile duo it is indeed wise to understand where AI research goes and which ways are available to mitigate certain risks. The same as line of thought being applied to nuclear bombs technology. One approaches for risk mitigation is to think about more resilient infrastructure for the next centuries where it won’t be easy for a machine to seize control on critical infrastructure and enslave us.
  • 17. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Now it is 5th of August 2016, few hours after the competition ended7 and it seems that mankind is intact. As far as we see. References 1 https://cgc.darpa.mil/
 2 https://www.defcon.org/html/links/dc-ctf.html 
 3 http://observer.com/2015/08/stephen-hawking-elon-musk-and- bill-gates-warn-about- artificial-intelligence/
 4 https://www.inverse.com/article/18301-elon-musk-warns-that- darpa-artificial-intelligence- security-challenge-will-yield-skynet
 5 https://en.wikipedia.org/wiki/Skynet_(Terminator)
 6 https://www.reddit.com/r/AskScienceFiction/comments/ 1ntco1/ the_matrix_revolutions_why_not_use_emp_to_defend/
 7 https://twitter.com/daniel_bilar/status/761396166181416961
  • 18. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 The Bioengineering track Theme leader: Dr. Elishai Ezra Tsur
  • 19. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Abstract Seeing beyond our own eyes: a new world of data and images captured from beyond the visible spectrum by the human eye can be used to recognize unique ID patterns to all kinds of substances existing today on Earth or even in Space. Welcome to the Hyperspectral Imaging world that promises to look again, in a different way, on everything around us. A big group of imaging technologies that have been gaining leverage in the market with the development of more amazing tools in computer vision and big data. Introduction Understanding the technologies in this field encapsulates the possibility to understand changes in three main aspects of our lives: First, HIS (Hyperspectral Imaging System) are already impacting Health. The traditional diagnosis, data analysis of patients and even surgeries have already being improved by this non-invasive method of imaging. The same method is used in the food industry that has been able better differentiate products and soon will be impacted by the access individuals will have to hyperspectral cameras and the insights gained from their analysis. Second, we’ll talk about how how new technologies change the way we work and live as a community and society and design our systems to provide for us. With its pros and cons, HIS as a technology promises to bring new insights about our surroundings with a potential to change the way we live our lives. Last but not least, this technology is helping us to understand big and large spaces such as crops, forests and cities. The impacts on the optimization of agriculture, for instance, are starting to show with the overlap of this imagings and sensors on the soil, many optimizations HyperSpectral Imaging and Social Impact Chen Mor, Ernesto Ferreira, Mariana Fonseca, Palak Dudani
  • 20. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 and analysis can be done. Pollution and global warming are a part of a group of big problems that can be monitored and analysed much better. On the other hand, looking up and out of our Earth can help humanity improve its understanding of materials and processes in universe and increase our knowledge about the outer-space, a topic that fascinated humanity for generations. Defining the Technology Hyper-Spectroscopy, or Hyperspectral Imaging, is the collection and processing of information from across the electromagnetic spectrum. It measures a wide part of the spectrum, divided to a lot of narrow bands, with high resolution. The definition of a wide part of the spectrum and high resolution is usually in comparison to the human eye and the visible spectrum (which includes 3 bands - red, green and blue). This term could refer to a big variety of technologies, each one measuring a different part of the spectrum in different ways. Because every substance in the universe has a unique pattern of emission and reflection of electromagnetic waves this technology is being used in a lot of different fields including agriculture, food processing, earth science, astronomy, chemistry, health and more. Techniques One technique is simply taking a snapshot, a method that does not include scanning (also called non-scanning). In this method only one picture is taken. The advantage of this method is that there is much less information to process, and therefore it requires less time, memory and all the resources they require. The disadvantage is that the outcome is only a 2D picture and in many cases it is not sufficient information. Another technique is spatial scanning. In this technique one records all of the bandwidth of a 2D picture, meaning a hyperspectral 2D picture, and then takes a lot of these pictures and uses computer vision algorithms in order to create a complete 3D hyperspectral image. It has the advantage of a theoretically analog quality regarding the wavelengths measured. The disadvantage is that it requires saving and processing a lot of information. Yet another technique is spectral scanning, in which monochromatic 2D pictures are taken. The monochrom can change in wavelength using different filters. It has the
  • 21. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 advantage of allowing a very good control on the spectral bands, but the disadvantage of also requiring relatively high amounts of processing and memory. An additional technique is spatiospectral scanning, which combines both spectral and spatial scanning. Therefore it combines their advantages and disadvantages, depending on the way the measuring device is built and used. Technological limitations While hyperspectral measurement and analysis are constantly improving, the needs of various technological fields from the technology also constantly grow and evolve. The main needs of the industry at the moment are better resolution, that is needed for separation between small objects in satellite pictures for example, better usage of memory and processing power and cheaper equipment. As mentioned the technology improves and satisfies more and more needs along with the improvements in the fields of computer processing, optics, computer vision, picture processing and even quantum physics. The Lone Human The Premise We are going to know almost everything about ourselves in the next few years - understanding our body, how it works, what makes it stronger, what makes us less productive and how to prolong our lives. Hyperspectral Imaging (HSI), in an individual point of will, can be, first of all, place in this society trend of "quantifying self" and habits of life quality improvements. In one hand, we have been seeing HIS been used in the past decade to improve diagnosis and image-guided surgeries and also to better differentiate good and bad quality of food (fruits, grains, etc.) in industries. But as the technology starts to decrease its price and become more accessible, we start to see more usages in prevention of illness and improvements in quality of life, nutrition and exercise habits for instance. Medical applications Spatially resolved spectral imaging obtained by HIS provides diagnostic information about the tissue physiology, morphology, and composition which offers great potential for noninvasive disease diagnosis and surgical guidance. In recent
  • 22. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 years, advances in hyperspectral cameras, image analysis methods, and computational power make it possible for many exciting applications in the medical field. A few examples of applications are: Cancers
 The key for cancer detection through Hyper Spectral Imaging (HSI) is the fluorescence properties of tissues. The biochemical and morphological aspects to the lesions alter the absorption, scattering and fluorescence properties of the tissue . As result the image improves and provides enough information for a valuable diagnostic. Image analysis enables the extraction of diagnostically useful information from a large medical hyperspectral dataset at the tissue, cellular, and molecular levels and therefore is critical for disease screening, diagnosis, and treatment. Brain cancer, breast cancer, skin cancer and many other types of cancer have been diagnosed and followed through treatment with HIS. Heart and circulatory pathology
 Each year, one in every four deaths in the United States is caused by a heart disease. HIS has been explored in heart and circulatory pathology in different ways in vivo or in vitro. One of the interesting result of its use is the capability of in an noninvasively way analyse the peripheral arterial disease better than traditional methods. Using HIS it is possible to analyse the level of oxygenation of the arteries and therefore the potential developments and also the progress of treatments. Surgery Guidance
 During a surgery, the success of the operation critically depends on the doctors being able to make the right judgments identifying the organs, tissues and the lesion to be treated. For that they need to see and feel the tissues and organs despite the blood that can be a big obstacle. HIS has being used to help as an intraoperative visual aid tool. Just for starts, they can help understanding the tissue structure and position even though it is submerged in blood. HIS is also used to help doctors identify cancerous tissues during surgeries in order to remove tumors successfully. Furthermore, doctors could, in addition, understand the reminiscences of cancerogenous tissues, maximize the tumor removal and minimize the risks of recurrent tumors.
  • 23. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Food
 In the Food Industry, the big first market for HIS started with the combination of imaging and intelligent softwares that help companies sort between good and bad products going through their production lines. HIS is helping to differentiate defects and foreign materials in the food that are not detectable by human eyes or any traditional camera. The next step might be giving this power to the final consumers once the prices of having HIS cameras in your phone, for instance, keep dropping. Industrial use
 One of the best use cases of HIS in the Food industry is the imaging sorting of nuts in the production line. With this non- destructive method, it is possible to evaluate 100% of the products to separate stones, shells and other foreign material. The use of the method was improving the quality and decreasing the time invested in the process and was lowering costs and prices. The cameras have even been used to evaluate extraneous vegetable matter from walnuts, almonds, pistachios, pecans and other nuts. Commercial adoption of hyperspectral sorters is also advancing at a fast pace in the potato processing industry where the technology promises to solve a number of outstanding product quality problems. Most of the use cases are related to analysing problems and marks related to pests common in the crops. If it will work for potatoes and many other cultures might benefit of the differentiation of high and low quality vegetables/fruits and the effects not only of plagues but also pesticides But what is the impact of all of that in the human level. For starts, better quality and analysis of the food we are eating throughout the world. Butwe will also be able to have more control in our hands with the scale of the technology as we will see in a quick exercise of future use in the next section. Self use
 The power of differentiating good and bad food and also understanding health conditions might not be something only for technicians and doctors. All the use cases mentioned in this section for the industry and medical might soon become accessible in a personal level. With cameras of HIS getting cheaper, in our smartphones (or any IoT), and more computer vision algorithms becoming simpler and user friendly, the power of that kind of analysis could be at home, at the supermarket or in rural areas with poor access to expensive
  • 24. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 technology. A good example of these possibilities is SCiO, an israeli startup named Consumer Physics that is creating a hand sized portable molecular scanner that is aiming to let you know how old is the apple that you are about to buy or , for the near future, they've been working in measuring body fat. In large use, SCiO is still in the pre-order stage and has much to prove concerning its accuracy in usages possibilities, but starts to give us a glimpse of what the future could look like. HIS could be used on the day-to-day basis to analyse your body – what kind of minerals, antioxidants and health conditions you have at any given moment and what can you do to help you improve your life quality and avoid certain problems. If one of the solutions is eating some nuts or vegetables, you could be able to walk into a supermarket and check for yourself that the quality of the products is satisfies you before buying. You could check for pesticides vs organic, state of deterioration, amount of vitamins, etc. A few of these ideas are still high cost, need strong computers and large data storage to analyse the information. But as one more potential scenario of use case for the future of quantified- self generation, creating this uses implicates on the understanding the positive aspects and also the negative impact of controlling all this data and actions. Who would own all the personal data you could be generating? Would we, in an individual level, be ready to make the best decisions for our health only by interacting with computers? With no need for doctor? Are we going to be addicted to this uber quantified-self world? Effects on Community and Possible Social Ramifications Hyperspectral spectroscopy as giving access to a larger and more detailed set information on everyday consumable products. People would be not just able to use this information in everyday use, but also be able to derive meaning out of such interaction and eventually this will become the new baseline. Would we live differently and how would our lives change as these technologies become more integrated with our everyday lives?
  • 25. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 The Identification of Self What started out with touch based sensors being able to detect a touch event and simultaneously recognize complex configurations of the human hands and body during touch interaction.[1] But as the technology evolves, researcher have used HIS for novel two-dimensional feature space which uses the spectral absorption characteristics of melanin, hemoglobin and water to better characterize human skin. They used feature spaces to key in on specific constituents of human tissue by using a skin index concerned with how water and melanin’s presence in skin manifests at two different wavelengths in the near-infrared region.[2] This coupled with computer vision and using active learning strategies to provide an interactive robust solution would help reach high accuracy in a short training/testing cycle.[3] These changes would cut the overall cost of hyperspectral-based search and rescue systems by a factor of seven. Apart from physiological signs, Hyperspectral imaging (HSI) technique to extract the tissue oxygen saturation (StO2) value as a physiological feature for stress detection. Since traditional stress detection methods are contact-based and require sensors to be in contact with test subjects, the experimental results for this study showed that this new feature may be independent from perspiration and ambient temperature, ie. StO2 level could serve as a new modality to recognize stress at standoff distances.[4] Safety, Defence and Insurance In recent years, many target detection techniques in hyperspectral imagery have been widely investigated and have proven valuable in many applications including search-and- rescue operations, border surveillance, and mine detection. High spectral/spatial resolution sensor data are used for detection, classification, identification and tracking[5]. Anomaly detection methods [6] with no a priori knowledge represent a current field of scientific research for the hyperspectral imagery and pattern recognition communities [...] An anomaly detector enables one to detect targets whose signatures are spectrally distinct from their surroundings. In general, such anomalous targets are relatively small compared to the image background and only occur in the image with low probabilities. Even for smaller urban spaces, man made structures and environment can pose a challenge.
  • 26. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Classifying infrastructure involves identifying materials that can be used for more than one purpose, for example concrete and gravel [7]. Apart from urban areas, organizations like SSC San Diego work with DARPA’s Adaptive Spectral Reconnaissance Program (ASRP) with the goal to demonstrate the detection of concealed terrestrial military targets and the cueing of a high-resolution imager. They use it for terrestrial Hyperspectral Remote Sensing which is described as the capability to detect military targets of interest in real time. This is done using an airborne hyperspectral system to cue highresolution images for ground analysis. Another area is Maritime Sensor Systems where the data is again evaluated in near real time using both spectral and spatial processing, providing "frozen" display of the target along with its position in longitude and latitude. [8] Medicine Scanning for the contents of drugs a huge impact on health market. This would change the way we also consume drugs? What about illegal drugs would we be tempted to use this on all product and what would counterfeiting look like mimicking false biosignatures? What would be the repercussions of such a thing on a community? Detection of simple diseases like urinary tract infection [9] could become very cheap and easy to do because of lower manpower and lower costs of microbial detection, with huge scope of impact on rural areas (esp in India) where the means of identification and diagnosis are economically and infrastructurally inaccessible to the poor. Another seminal work covers optical imaging techniques for early diagnosis and monitoring of hypercholesterolemia. Characterized by high levels of cholesterol in the blood, it’s associated with an increased risk of atherosclerosis and coronary heart disease. In india, where a person succumbs to heart attack every half a min[10], early detection of hypercholesterolemia could prove life saving. Food Consumption Quality Control: could be modified for detection and identification of foreign objects among raw material samples, for example, in a food processing chain.[11] With the outbreak of the milk powder scandal (addition of melamine) in China in 2008 and the more recent meat adulteration scandal [12] the
  • 27. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 detection of adulterants and consideration of appropriate detection methods received renewed attention. Disassociation of ‘Outside Image’ and Nutrients: Sorting of fruit based on quality attributes and not only on external appearance, has become a reality due to the availability of NIR spectrophotometers.[13] The short analysis time (seconds) required by diode array instruments also enables on-line sorting of fruit based on quality properties. In spite of NIR spectroscopy being an economical technique (once implemented), it will be costly to replace current systems (based on visual external appearance evaluation of fruit and vegetables). It will thus only become feasible to implement NIR spectroscopy on-line once consumers are willing to pay higher prices for fruit being e.g. extra sweet. Differentiation from ‘Best Before’: Quality aspects important for fresh fruit and vegetables include measurement of firmness and SSC with detection of early bruising and chilling injury also being important. One of the most significant benefits of NIR hyperspectral imaging is that defects such as bruising can be detected and visualised in principal component images or classification plots before they are actually visible on the fruit itself. This enables the opportunity to prevent fruit and vegetable with potentially short shelf-life to enter the supply chain.[14] The Brighter Side: Recycling, Optimisations and Super Humans Used plastic packaging and other plastic items can be valuable resources in the manufacture of new products and in the generation of energy difficult to separate and chemically incompatible. In order to produce high purity granulates from these concentrates, of a quality comparable to materials produced from post-industrial waste, the mixture must be sorted very accurately though they involve multiple separations and are therefore expensive. The identification of contaminants in secondary plastics, adopting HSI, thus can represent a first attempt to introduce an innovative polyolefins separation process from end-of-life product, connecting technical capabilities (contaminants identification) with societal market needs (quality of the recycled products and lowed cost).[15] This technology can be profitable used in the recycling sector both as smart detection engine for sorting and/ or as flow stream quality control. Combined with Magnetic
  • 28. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Density Separation (MDS), to turn them into a profitable green business.[16] Optimisation in the food industry could mean fighting adulteration, maintaining high quality and making sure the food is judged based on its nutrients and how it looks on the outside. This could have a significant impact for the community at large as half the food produced in US today is thrown because it looks ugly.[17] Would this change the food industry? What impact could it have on the distribution of food among the have and have nots? Other industries like paper processing environment where the water content of the paper is a critical parameter, a near-infrared spectral imaging system in real-time could measure, analyzes and report the moisture content of the paper. This allows the plant control system to automatically adjust its operating conditions for optimum throughput of production and uniform quality of paper. Reducing hours of work to just a few minutes, HIS technique saves tons of paper and reduces manufacturing costs. [18] Low-cost hardware implementation of a hyperspectral cameras like HyperCam make hyperspectral imaging easier to implement and explore as a sensing modality. food quality monitoring and opening doors in multiple domains including health sensing and interaction systems.[19] While recognition in terms of bionic signature would become the new normal, what would tampering with a personal biosignature involve and how would modern thefts be different? Another view point offers an increase in capabilities - being able to work and use with more than what our bodies were naturally capable of [20]. Superflux worked with Dr Patrick Degenaar from Newcastle University - Using thermal imaging cameras (which allow you to see heat), Superflux made a film showing how previously blind people would be able to see the world. “It’s not high-resolution. It could be blurry but they are able to see the world in new ways.” A handset would then enable users to dial into the type of vision they wanted. [21] The Darker Shades: Commercialisation and Capitalism Scenario: Algorithmically-determined genetic risk profiling, and backstreet gene-fixing. The project's protagonist, Arnold Mann, is a 'regular guy' who finds himself in an impossible situation when a government DNA spit test causes an unaffordable rise in his health insurance contributions. Trapped
  • 29. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 between inflated premiums and the costs of private genetic therapy, Mann approaches a black market clinic. Treated with a bootlegged therapy, the cost of Mann’s insurance initially falls, but the illegality of his actions are quickly discovered, and evidence is gathered by the therapy's licence holder, Dynamic Genetics, in the case against Mann.[22] Our World - The View from Above The Premise If High Spectral Cameras can change the way we understand our body and our city; imagine the impact it can have in Global scale; developing this technology, sending in stats and bringing this information back the Earth are some of the challenges the researchers need to solve. Agriculture Agriculture may be one of our biggest issues for the next 10 years, how to make more food but with less impact and high efficiency. High Spectral Cameras have an important role to understand the problem and address a solution. One of the most recognized projects is the International Space Station Agricultural Camera (ISSAC)[23]- NASA - uses infrared and RGB photos from North American Great Plains - focusing in forests, farms, grasslands. This information take to days of processing and transmission until the farmers and researchers have access to it; helping them to understand about planning, fertilizer and pesticide application. This understanding can help avoid ecosystem damage by reducing overgrazing and erosion. Ranchers will be better able to determine livestock carrying capacity of rangelands; this can help avoid ecosystem damage due to overgrazing and erosion. Scientists will gain new knowledge of rapidly-changing phenomena, observing phonological response to daily changing conditions. Geographic locations around the globe that are frequently under cloud cover during overflights of existing sensors will be able to be observed at times more conducive to cloud-free imaging. Environment Another application, connected with this first, is the MODIS[24] project - NASA, which is an international team
  • 30. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 that aims to study about Atmosphere[25], Oceans[26] and Land[27]. The MODIS project uses static maps to develop a global map in seasonal representation with specific wavelengths of interest. Aiming to increase it impact, MODIS has shared its projections within the society. One of the challenges in this project is the size of the data, we are working with different photos in global scale; what makes harder to storage and - manly - to send back to Earth. To solve this issue they used of different methods, since reducing the number of photos per day from 300 to 10, reducing the pixel definition to 1 pixel per Km and excluding irrelevant areas; but using metadata they made the biggest difference: they reduced in 95% the size of the data.[28] Calibration One of the most challenging tasks in remote sensing from space is achieving instrument calibration accuracy on-orbit, to solve this problem we have used our natural satellite: the moon. In fact, it’s a stable option, in the past 10 years the stability derived from the lunar time series, is 0.13%. However, the current accuracy of the Moon as an absolute reference is limited to 5 – 10% and this variation increases the risk of lunar maneuvers. To solve this problem the ARCSTONE project (it is starting in 2016) used an orbiting spectrometer flying on a satellite in LEO (Low Earth Orbit) to provide lunar spectral reflectance. Positive and Negative aspects The best aspect of High Spectral Cameras are the amount of information on time, providing us a real time world wide look we have never had. Using this different spectrals it is possible to see chemical composition of the air, forests and soil. And More than the direct impact of all this data we need to remember the impact the connection of this data. Imagine what we can learn connecting Forests and CO2[29] concentration, the connection between albedo and the wavelength to understand the kind of forest and more. Some studies estimate the economic impact of establishing highly accurate Earth climate observations is at $12 T over 40 to 60 years.[30] In other hand, all this information that impacts with everyone’s life can be dangerous. Since companies burning food to increase the price based on future (safras) to hackers that can
  • 31. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 change the information and drive the market and our vision from reality. But more than that, in a possible cyber war governments can try to use this technology as an army tool, using it to recognise enemies and hide important information. Conclusion The wealth of additional information available and the application benefits that hyperspectral imaging produce are almost without limit. Since its early use in satellite remote sensing, both the technique and optical instrumentation have developed to support applications that require real-time process monitoring, control, inspection, quantification and identifications. The use of transmission-grating imaging spectrographs has allowed these systems to be compact and robust and to possess excellent spatial and spectral performances at a cost level not easily matched by comparable instrumentation. It can be expected that the growth in hyperspectral imaging will continue in chemical monitoring, whether it is the life sciences, forensics, homeland security, pharmaceuticals or any other application where the spectral information provides a dramatic contrast improvement in sample conditions and features compared with conventional imaging systems. References [1] Touché: Touch and Gesture Sensing for the Real World (https://www.disneyresearch.com/project/touche-touch-and- gesture-sensing-for-the-real-world/) [2] Human Skin Detection Technology for Improved Security, Search and Rescue (http://www.osa.org/en-us/about_osa/ newsroom/news_releases/2015/ human_skin_detection_technology_for_improved_secur/ [3] Person detection in hyperspectral images via skin segmentation using an active learning approach (https:// utep.influuent.utsystem.edu/en/publications/person-detection- in-hyperspectral-images-via-skin-segmentation-us [4] Detection of Psychological Stress Using a Hyperspectral Imaging Technique (https://www.researchgate.net/publication/ 273396321_Detection_of_Psychological_Stress_Using_a_Hypers pectral_Imaging_Technique)
  • 32. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 [5] Detection in urban scenario using combined airborne imaging sensors (http://proceedings.spiedigitallibrary.org/ proceeding.aspx?articleid=1353408) [6] Anomaly Detection for Hypaerspectral Imagery Using Analytical Fusion and RX (http://bit.kuas.edu.tw/~jihmsp/2014/ vol5/JIH-MSP-2014-02-006.pdf) [7] Enhanced hyperspectral imaging for urban reconnaissance (http://spie.org/newsroom/4834-enhanced-hyperspectral- imaging-for-urban-reconnaissance) [8] Hyperspectral Imaging for Intelligence, Surveillance, and Reconnaissance David Stein, Jon Schoonmaker, and Eric Coolbaugh (http://www.dtic.mil/dtic/tr/fulltext/u2/a434124.pdf) [9] Hyperspectral imaging for presumptive identification of bacterial colonies on solid chromogenic culture media (https:// www.researchgate.net/publication/ 303313926_Hyperspectral_imaging_for_presumptive_identificat ion_of_bacterial_colonies_on_solid_chromogenic_culture_med ia) [10] Heart attack kills one person every 33 seconds in India (http://timesofindia.indiatimes.com/life-style/health-fitness/ health-news/Heart-attack-kills-one-person-every-33-seconds-in- India/articleshow/52339891.cms) [11] Near infrared hyperspectral imaging for foreign body detection and identification in food processing (https:// www.researchgate.net/publication/ 286599610_Near_infrared_hyperspectral_imaging_for_foreign_ body_detection_and_identification_in_food_processing) [12] Application of hyperspectral imaging in food safety inspection and control: a review (http://www.ncbi.nlm.nih.gov/ pubmed/?term=22823350%5Buid%5D) [13] Nondestructive measurement of fruit and vegetable quality by means of NIR spectroscopy: A review (http:// www.sciencedirect.com/science/article/pii/S0925521407002293) [14] Principles and applications of hyperspectral imaging in quality evaluation of agro-food products: a review (http:// www.ncbi.nlm.nih.gov/pubmed/?term=22823348%5Buid%5D)
  • 33. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 [15] The Utilization of Hyperspectral Imaging for Impurities Detection in Secondary Plastics (http://benthamopen.com/ contents/pdf/TOWMJ/TOWMJ-3-56.pdf) [16] Turning Magnetic Density Separation into Green Business Using the Cyclic Innovation Model (http://benthamopen.com/ contents/pdf/TOWMJ/TOWMJ-3-99.pdf) [17] Half of all US food produce is thrown away, new research suggests (https://www.theguardian.com/environment/2016/jul/ 13/us-food-waste-ugly-fruit-vegetables-perfect) [18] Hyperspectral Imaging Spectroscopy: A Look at Real-Life Applications (http://www.photonics.com/EDU/ Handbook.aspx?AID=25139) [19] HyperCam: Hyperspectral Imaging for Ubiquitous Computing Applications (http://homes.cs.washington.edu/ ~mayank/Papers/HyperCam.pdf) [20] Blind Mice Recover Visual Responses Using Protein from Green Algae (https://www.nih.gov/news-events/news-releases/ blind-mice-recover-visual-responses-using-protein-green-algae) [21] Superflux founder Anab Jain on using technology to turn the blind into super-seers (http://www.standard.co.uk/lifestyle/ london-life/superflux-founder-anab-jain-on-using-technology- to-turn-the-blind-into-superseers-a3278941.html) [22] Dynamic Genetics Vs. Mann (http://www.superflux.in/ work/dynamicgenetics) [23] International Space Station Agricultural Camera (ISSAC) (http://www.nasa.gov/mission_pages/station/research/ experiments/81.html) [24] MODIS (http://modis-atmos.gsfc.nasa.gov/index.html) [25] MODIS - Atmosphere (http://modis-atmos.gsfc.nasa.gov/) [26] MODIS - Oceans (http://oceancolor.gsfc.nasa.gov/cms/) [27] MODIS - Land (http://modis-land.gsfc.nasa.gov/) [28] Eric G. Moody , Michael D. King, Steven Platnick, Alan H. Strahler, Crystal Schaaf , Feng Gao, -> Valued-Added Albedo and Ecosystem Products Derived [29] MCST (http://mcst.gsfc.nasa.gov/)
  • 34. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 [30] (Cooke, “Value of Information for Climate Observing Systems,” Environ. Syst. Decis. 2014. ) Chein-I Chang (31 July 2003). Hyperspectral Imaging: Techniques for Spectral Detection and Classification. Springer Science & Business Media. ISBN 978-0-306-47483-5. Jump up^ Hans Grahn; Paul Geladi (27 September 2007). Techniques and Applications of Hyperspectral Image Analysis. John Wiley & Sons. ISBN 978-0-470-01087-7. Medical hyperspectral imaging: a review - Journal of Biomedical Optics – J. Biomed. Opt. 19(1), 010901 (Jan 20, 2014). doi:10.1117/1.JBO.19.1.010901 https://www.consumerphysics.com/ (27, july, 2016)
  • 35. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Abstract In this paper we intend to give an overview of the current brain biotechnology and computer researches that has been developed, such as neuroprosthetics, brain on a chip and artificial neurons. By projecting brain current achievements into the future, we will try to indicate the implications that might be possible regarding enhancement of brain capabilities and curing brain damage. Part I: Introduction Technological and physical assumptions overview In this paragraph, we would like to establish our theory using few main leads that are currently being studied and implemented at brain science field: The brain as a physical structure In this article we would lean on the established assumption at brain science field, which claims that the physical structure of the neural network of the brain affecting its functionality.
 This led us to think that the role of of each part of the brain can be somehow reconstructed, using tools that reconstruct the physical structure of the neural network. In addition, regarding the BNN (Brain’s Neural Network) as a physical structure, have also lead to the conclusion that information at the BNN is being transferred as electrical signals. Analyzing and monitoring these electrical signals have been performed in many different scales and tools, using technologies such as Electroencephalography (EEG) which will include analyzing the different wavelengths emitted by the brain, fMRI , fNIRS, PET, etc. In our article we will consider the size of the Neurons as 4 to 100 micrometers (106) in diameter, and refer to the nanoscale A Brain in a Lab Inbal Levi, Catarina Papa
  • 36. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 of the electrical signals. We also assume the ability to transfer signals BNN. In addition, we will use tools from Graph theory, and refer to the neurons as nodes, connected at a neural network, in a similar way that is represented in the article Graph theoretical analysis of complex networks in the brain (Cornelis J Stam and Jaap C Reijneveld, 2007) Growing brain structures “on a chip” Due to new technology advancements, there is some studies entering in the possibilities of growing brain structures on a chip with the purpose of understanding neural disorders. The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Dr. Madeline Lancaster from MRC Lab developed a new model system called cerebral organoids. Cerebral organoids, or minibrains for short, are 3D tissues generated from human pluripotent stem cells that allow modelling of human brain development in vitro. Through a process of directed differentiation and a supportive 3D microenvironment, neural precursor tissue can spontaneously selforganize to form the stereotypic organization of the early human embryonic brain. (Madeline Lancaster, 2013) In the Tissue Engineering Resource Center at Tufts University, Boston USA, Bioengineers have created threedimensional brainlike tissue. The functions like and has structural features similar to tissue in the rat brain. The tissue engineers use 3D gel environments to create and establish freely connections in all directions and the brain and also can be kept alive in the lab for more than two months. The technology advancements reached to maintain this tissue for months in the lab allow them to look for neurological diseases. ( Fu%s University, 2014) The researchers have been using the brainlike tissue to study chemical and electrical changes that occur immediately following traumatic brain injury and also, to study changes that occur in response to a drug. In the University of Florida, USA, scientist has grown a living “brain” that can fly a simulated plane. The “brain” was taken from a rat’s brain and cultured inside a glass dish. In the same direction, the purpose of watching the brain cell interactions is
  • 37. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 to understand the causes of neural disorders. (Thomas DeMarse, 2005) Brain Sensing Technologies As a result of prof. Dvir Tal, from Tel Aviv University, we assume it is possible to implement passive sensors inside the BNN in order to collect the feedback about brain activities patterns, hopefully, without harming the BNN electrical pattern. Neural Networks Artificial neural networks As an example of this transdisciplinary solution, Kwabena Boahen, an associate professor in the Department of Bioengineering of Stanford, has been directing a research group tasked with mimicking the functions of the brain's complex neural system using silicon chips. Connecting a large amount (approximately 10 5 ) of artificial neurons to a multiplechip network that gets up to about 1 million neurons. Considering the network size, it is possible to differentiate cortical areas and study how they are talking to each other. Boahen hopes his research will lead to small computers that could replace damaged neural tissue or silicon retinas that restore vision. He believes understanding how the brain functions could help make computation more efficient. The work of T. W. Berger and others (brainimplantable biomimetic electronics as the next era in neural prosthetics, that was published at the IEEE Journal, they have managed to create a silicon chip that is capable of interacting with a neural network. Another development regarding artificial brains was made by IBḾs accomplishment is significant once faux neurons are built out of wellknown materials and they are able to scale down to a few nanometers.
 Organic neurons have membranes acting as signal gates. The energy needed to activate computer, has made it impossible to maintain in vivo, but IBM’s recent development have made it possible. (David Lumb ,2016) With these neurons, scientists may be able to create computers mimicking the efficient, parallel processing design of organic
  • 38. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 brains and apply its style of approach to decisionmaking and processing information. Computer ScienceApplications A different application of the neural network is to demonstrate distributed system. The brain have strong capabilities, and by imitating the structure we are now able to solve complex computational problems.
 The main key feature of such a network would be speed (due to the parallel processing). Some of implementations are the neural network algorithm, and the deep learning method, both have enabled faster data processing. Brain-computer Interface There are two general approaches for braincomputer interfaces implementation: invasive or partially invasive interface which imply physical interaction with neurons, and noninvasive based on electroencephalography (EEG) and functional MRI.
 Due to its cortical plasticity brain can also adopt to handle external signals, which opens opportunities for neuroprosthetics and researches of brain activities. Part II: Possible implementations and use cases In this paragraph we would go briefly over some known use cases, and than suggest new use cases for the technologies mentioned above: Future use cases:
 Using brain damage tissue reverse. According to Dvir lab research, implementing active sensors in order to modify brain’s electrical network is possible. We claim that it would be possible including sensors inside a damaged brain tissue (considering it have no functionality as a result of the damage) and understand what is missing in the neural network pattern. Than, by building a neural network using the patient’s tissue, hopefully, we would be able to reconstruct the damaged part, and impliment it back to the damaged brain, in order to restore functionality. Implementing active sensors to fix brain damage after diagnosis: Though it’s still haven’t been done in humans, It is possible now to construct a personal fitted neural network by taking fat tissue from the person, modify the cells into neurons, developing it outside the body and implement it.
  • 39. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Another way to reconstruct neural network would be by encouraging the cells to reconstruct with injunction of materials. Regardless the method, with , the coordination between the implemented tissue and the current tissue is yet to be perfect. Improving skills: By mapping the brain function using passive sensors mentioned above, we would suggest to mimic the patterns of gifted peoplés brain to improve existing skills or acquire new skills.
 The idea would be creating “neural soup” of neurons regarding the certain ability the user would want to implement or develop, and connect it back to your brain. Study with ML the features of the ability from existing humans and try to imitate its structure at the ANN developed for implementation, such as: You can figure out these parameters, and have an identification of the skill involved.
 And than you will be able to add these networks back to your brain, encouraging the skill to become. ANNArtificial Neural Network: the development of neural networks using small components that can We detect that it would also lead to increment of Neuroprosthetics creating and implementing artificial brain sensors and stimulators and this track leads to neuroprosthetics, which is artificial neural implants. Regarding constructing the electrical pattern, we suggest that it might be possible using ML methods to learn the missing parts patterns from other brains. Part III: Conclusions and Further Thoughts In spite of the fact that today we dońt have the technology and that there is many developments that we can not predict, we should consider the technology enhancements that currently exists and conclude that it might open a window to a great deal of possibilities. Considering the improvements in the brain on a chip studies and developments, we would also like to state some further implications that might be possible in the future: Transform consciousness to artificial brain, and back to biological body. Make biological changes to extend life or stay younger, in the brain structure or tissues. Brain’s electrical signals sending data to the world with our brains.
 The expected form of a post human body.

  • 40. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Neural network based computer, and its effect on software world and real world Regardless thouse predictions will come to fulfil or not, it is obvious that the main machine that controls all of our activities would soon be able to change more than ever befor. References (1)  Cornelis J Stam and Jaap C Reijneveld (2007) Graph theoretical analysis of complex networks in the brain, Nonlinear Biomed Phys.
 www.ncbi.nlm.nih.gov/pmc/articles/PMC1976403/ (2)  Arlingron hewes (2014) Experimental Rat ‘Brain’ Fighter Pilot May Yield Insights Into How the Brain Works, singularityhub website singularityhub.com/2014/09/04/ experimentalratbrainfighterpilotmayyieldinsightsintohowthe brainworks/ (3) T. W. Berger, M. Baudry , R. D. Brinton , J. S. Liaw , V. Z. Marmarelis , A. Yoondong Park , B. J. Sheu , A. R. Tanguay, (2011) Brainimplantable biomimetic electronics as the next era in neural prosthetics (4)  (2014) Fufts University, Boston www.nibib.nih.gov/news- events/newsroom/bioengineerscreatefunctional3dbraintissue (5)  Thomas DeMarse, University of Florida www.research.ufl.edu/publications/explore/v10n1/extract2.html (6)  David Lumb (2016) IBM researcher builds a phasechange capable artificial neuron www.engadget.com/2016/08/03/ibm- researcherbuildsaphasechangecapableartificialneuron/ (7)  Madeline A. Lancaster, Magdalena Renner, Daniel Wenzel, Josef M. Penninger & Juergen A. Knoblich (2013) Cerebral organoids model human brain development and microcephaly www.nature.com/nature/journal/v501/n7467/abs/ nature12517.html#affilauth , Nature 501 : (7467):373379. 

  • 41. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Abstract The CRISPR-Cas9 system is a recent breakthrough technology enabling many different applications in the field of genetic engineering. The CRISPR-Cas9 system is easy to design, specific and cheap, making it a disruptive technology in many fields, from medicine and agriculture to basic science. In this review, we will discuss the scientific background of the system, current and future applications in different fields and the ethical implications of these applications. Introduction In the past 60 years, our ability to genetically engineer biological systems and organisms has provided many advances in basic science, medicine and biotechnology (Doudna et al.). Some of the major applications in the different fields include the creation of model organisms and cell lines for research, drug and antibody manufacturing, gene therapy, food manufacturing, development of organoids and many more. In recent years, a number of genome editing technologies have emerged, including zinc-finger nucleases (ZFNs), transcription- like effector nucleases (TALENs) and the RNA-guided CRISPR-Cas9 nuclease system (Ran et al.). The first two technologies are based on a strategy of binding endonuclease catalytic domains to modular DNA-binding proteins, creating a DNA cleavage complex inducing DNA double strand breaks (DSB’s) (Ran et al.). Since the specificity of the genomic editing in these methods is based on protein-DNA recognition, the use The CRISPR/Cas9 Genetic Engineering System: A Review and Ethical Discussion Lital Friedman, Raymond Harari, Daniela Klaiman, Yael Levinson and Marcelo Lopes
  • 42. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 of modular DNA-binding proteins or specifically synthesized proteins is necessary. This makes both ZFNs and TALENs methods extremely complicated and time-consuming. In contrast, the specificity of the genomic editing in the CRISPR-Cas technology is based on Watson-Crick base- pairing, providing site-specific DSB’s using a programmable sgRNA (Ran et al.). This enables an easily designable, specific and efficient method for DNA editing, suitable for high- throughput and multiplex experiments (Ran et al.). The CRISPR-Cas system is an adaptive immunological mechanism found in many types of bacteria and archea, designed to fight off viral infections (Doudna et al.). There are 3 types of CRISPR-Cas systems, yet the general structure is comprised of a CRISPR (Clusters of Regulatory Interspaced Short Palindromic Repeats) locus and a Cas genes locus (Fig 1) (Doudna et al.). The CRISPR locus is constructed of short palindromic repeats interspersed with viral DNA fragments. The Cas genes locus found in close proximity to the CRISPR locus and encodes to proteins associated with DNA repair. The general protective mechanism of the CRISPR-Cas system is comprised of three main stages (Fig. 2) (Doudna et al.): First, the viral DNA injected into the bacteria upon infection gets cleaved into short fragments and incorporated into the bacterial CRISPR locus. Then, CRISPR-RNA (crRNA), a short RNA homologous to the viral RNA fragment is synthesized by the bacteria and a Cas9-crRNA complex is formed. Cas9 is a nuclease enzyme encoded by one of the Cas genes which induces double strand breaks in DNA. In the final stage, the Cas9-crRNA complex enables cleavage of the DNA only in the specific genomic loci homologous to the crRNA. This provides the bacteria the ability to block any future attack Schematic representation of the CRISPR locus in the bacterial/archaeal genome. Black hexagons represent short palindromic repeats and coloured rectangles represent fragments of viral DNA. Dark blue rectangle represents the cas genes locus.
  • 43. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 by the same virus, using its genetic code against it and degrading its DNA (Doudna et al.). Within this general process, the three CRISPR-Cas systems differ slightly in the molecular mechanisms and the specific Cas proteins needed of nucleic acid recognition and cleavage. However, it has been recently discovered that the CRISPR- Cas system type II requires only one Cas protein- the Cas9, for DNA recognition and cleavage. This important finding proved to be a major breakthrough in the field of genetic engineering, enabling researchers to easily adjust the bacterial system to perform DNA editing and manipulation in any model organism they desire (Doudna et al.). Today, the CRISPR-Cas9 method can be used in dozens of genome editing applications, from targeted mutations (Freedman et al.) to gene knock-out and knock-in (Pennisi et al.). For example, recent studies show the CRISPR-Cas9 can be used to cut from 5 to 62 genes at once (Pennisi et al.). Another interesting application is the CRISPR-interference (CRISPRi), a method that utilizes the CRISPR-Cas9 system for gene knockdown. This enables the researcher to reduce the expression level of a specific gene in a controlled way (Qi et al.). CRISPR-Cas9 system allows us to easily create model organisms that mimic a specific disease or show what happens when a specific gene is knocked-down, out or mutated. This The three steps required to acquire viral immunity in bacteria
  • 44. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 can be done at the germ-line level creating an organism carrying the modification in all the cells in its body, or it can be targeted to specific cell types (Liu et al.) Current CRISPR/Cas9 applications Correction of genetic diseases The CRISPR/Cas9 system has been used to correct disease- causing mutations in animals and in human cells. One of the first corrections of genetic diseases using CRISPR-Cas9 was performed in mice with a genetic mutation causing cataracts. Mouse zygotes carrying the dominant Crygc mutation were injected with Cas9 mRNA and a single-guide RNA (sgRNA) targeted to the mutant allele, which enabled correction of the mutated gene via homology-directed repair (HDR). These rescued mice were able to pass the corrected gene to their offspring (Wu, Yuxuan et al). Correction of genetic diseases in human cells is also possible using the CRISPR-Cas9 technology. For example, researchers were recently able to remove the HIV-1 genome from infected human CD4+ T-cells. Co-expressing Cas9 and two guide RNAs (gRNAs) which targeted conserved HIV-1 sequences caused complete inhibition of HIV-1 expression in these cells. In addition, the cells expressing Cas9 and the HIV-1 directed gRNAs were protected from new infections with HIV-1. These findings suggest that the CRISPR-Cas9 system may one day be used to eliminate HIV-1 in humans and cure AIDS (Kaminski, R. et al). The CRISPR/Cas9 system can also be applied in human pre- implantation embryos. A Chinese group was successful in editing the β-globin gene (HBB) in human zygotes and replacing it with the delta-globin gene (HBD) using CRISPR/ Cas9. HBB encodes a subunit of hemoglobin and is mutated in β-thalassemia; the HBD gene is very similar to HBB and can be used as a template to repair HBB. The researchers were able to replace the HBB gene with the HBD gene in around 14% of the embryos, but also found that the CRISPR/Cas9 had off target effects in some of the embryos (Liang, P., Xu, Y., Zhang, X. et al). This report, as well as reports of other groups conducting human embryo gene editing led to global debates over the ethics of using CRISPR/Cas9 in human embryos (Callaway).
  • 45. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Animal models Animal models are used today for research of many diseases, including cancer, diabetes and neurodegenerative diseases. As the CRISPR/Cas9 system allows simple and efficient genetic manipulation of genomes, it is currently used to create in vivo disease models. For example, CRISPR was used to generate cancer models in mice by targeting tumor suppressor genes pten and p53. In zebrafish, the CRISPR/Cas system was used to generate hematological disease by causing mutations in blood development genes (Ma D, Liu F.). CRISPR was also used to generate models of Parkinson disease in pigs. Loss of function in the following genes - Parkin, Pink1 and DJ1 - is known to cause PD; therefor by knocking out these genes using CRISPR it was possible to create a PD model. (Yang et. al.) As CRISPR can theoretically target any gene, it should be possible to easily generate animal models with specific gene modifications using this technology, once you decide which gene you’d like to target. Human cellular disease models As studying diseases in human models in vivo is not possible, one of the current ways to model human disease is using human cells, including induced pluripotent stem cells (iPSCs), in vitro. Combining CRISPR technology with the technology of iPSCs can allow generation of specific cell types with site- specific mutations. (Waddington et al.) For example, a recent study used CRISPR to cause mutations in human pluripotent stem cell derived kidney cells (hPSC-KCs) in order to model and study polycystic kidney disease. (Freedman et al.) Gene drive: Parasite resistance and species extinction CRISPR/Cas9 can be used to create transgenic species, and has recently been used to create transgenic mosquitoes carrying genes for malaria resistance. These mosquitoes were engineered to not only be resistant to the human malaria parasite, Plasmodium falciparum, but to also contain a gene drive mechanism, which highly increases the odds of the gene being passed to their offspring. A gene drive plasmid was engineered to target a specific integration site in the mosquito genome; the resulting mosquito carries a malaria resistance gene as well as CRISPR/Cas9 genes which enable the malaria resistance gene to be passed on to about 99.5% of the offspring. This method has been achieved in the lab, but so far has not been
  • 46. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 tested in the field.(Gantz VM, Jasinskiene N, Tatarenkova O, et al.) Gene drives can be used to create species with with resistance to a number of parasites,thus preventing spread of infectious diseases. Another application of gene drives is the engineering of sterile female mosquitoes; this would suppress the mosquito population so that it would not be able to transmit diseases such as malaria. (Nolan et al.) Agriculture Plant genomes can be edited with the CRISPR/Cas9 system to create more sustainable agriculture for the fast-growing population. One of the applications of CRISPR in plants has been to generate virus-resistant plants, such as crops that are resistant to BCTV (Beet curly top virus), TYLCV (Tomato yellow leaf curl virus), and MeMV (Merremia mosaic virus) (Khatodia, Surender et al). CRISPR has also been used to engineer wheat that is resistant to mildew (Wang et al), and there was recently a group that was used CRISPR to generate maize with improved grain yield in drought conditions (Shi et. a.). Future CRISPR/Cas9 applications The CRISPR/Cas9 process has developed the gene editing field at remarkable speed. This is mostly because the process decreased the price of an an expensive method and made it more affordable and scalable. This new price point allows entrepreneurs outside academia to be able to do gene editing, whereas in the past they were unable to do so due to monetary constraint. This in turn creates much more innovation in the space and it pushes the limit as to what this technology will be able to do. It’s now clear that this method’s potential reaches beyond DNA cleavage, thus its usefulness for genome locus- specific modification of proteins will only be limited by our imagination. This technology could play a big part not only in humans, but also in animals and plants. Humans The possibility of gene editing in humans is very broad. For many years, scientists have longed to find a way to edit human and even embryonic genes, in order to “design” a person to their liking. For instance, through gene editing, one could change eye color, hair color, or any faction of a human being one desires. Additionally, this method could be used to re- engineer human DNA in order to avoid genetic diseases.
  • 47. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Taking it a bit further, this technology could create a human “debugging” system, whereby all humans are tested by it to determine that their genetic composition is healthy. This could potentially extinguish many of the genetic diseases we currently know and fear. Another use gene editing could have in the future is the creation of a “super-human”. Potentially, scientists will be able to exaggerate certain genes, in order to have them reflected in humans, even though naturally it hasn’t ever been seen before. For instance, they could modify humans to be extraordinarily strong, or to consume nutrients more efficiently. The sky's the limit for what this technology could achieve. Animals and Insects Similar to human applications, the CRISPR technology could also be used for animal enhancement. It would be possible to protect endangered species by modifying their genes and making them more resistant to changes in the environment. CRISPR/Cas9 could also be used to create new generations of livestock, with the needed characteristics to survive in specific environmental conditions. This will allow them to be more productive and resilient, giving them the ability to be engineered according to consumers’ desires, with custom features such as texture, taste, and nutritional value. Even the basic materials industry could benefit from ‘engineered’ animals that could, for instance, produce a stronger and more vivid leather. Recombinetics, a tech startup, is now working on Brazilian beef cattle engineered to have larger muscles to produce more meat. Other firms are developing chickens that only produce female offspring in order to lay more eggs and cattle that only produces male offsprings to have more efficient feed-to-meat conversion. One of the most revolutionary and impactful uses of CRISPR/ Cas9 is the elimination of insects that carry pernicious global health diseases, including malaria, dengue fever, sleeping sickness, yellow fever, West Nile virus, and Lyme disease. For instance, genome edited AedesAegypti, the Zika virus carrier, could be spread out to reproduce and generate infertile new mosquitos, which would eliminate these species in a short period of time.
  • 48. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Plants and Vegetation Genetically modifying crops with current methods is expensive, time demanding, and difficult. Not to mention, it’s hard to obtain FDA approval for use. Thus, most of the vegetation that has been modified in the past has been commodity crops such as corn and soybeans. CRISPR/Cas9 provides a tool to produce plant modifications at a faster pace and cheaper price. Plant enhancement would be one of the most common CRISPR/Cas9 applications, creating more productive, resistant, and efficient crops. These crops would require less strategic resources, such as water and land. It would be possible to modify plants and other vegetation to display different shapes, colors, flavors and to make them easier to be consumed. Alternatively, through CRISPR/Cas9 we could add nutritional value to delicious foods in order to make them healthy. On the other hand, genetic modification could be used not just for improvements but also for the elimination of weeds and other pathogens that disturb agriculture. Imagine a future where we could have cheap, resistant, and efficient plants to match the environmental requirements and consumers demands. That’s a future in which we’ll be able to harvest crops in the most inhospitable environments in the world, or maybe even on Mars. Takeaway Message It’s important that this technology remains on check. The possibilities unlocked by this affordable method are endless, and could end up compromising the world as we know it. It’s necessary to find a balance in this technology, because if it gets out of hand, it could be used by bad people to destabilize the world and do a lot of harm. Hank Greely, a bioethicist at Stanford, summarized the situation best: “Genome editing started with just a few big labs putting in lots of effort, trying something 1,000 times for one or two successes, now it’s something that someone with a BS and a couple thousand dollars’ worth of equipment can do. What was impractical is now almost everyday. That’s a big deal.”. This newfound efficiency and low cost will enable innovation to move very quickly, enabling us to reach heights we could only dream of before.
  • 49. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Ethical Implications CRISPR/Cas9 is a relatively new technology and as such it provides many opportunities but holds many risks as well. To quote Donald Rumsfeld on a different matter, the assessment of the former and latter may prove to be a very difficult task: “...there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns – the ones we don't know we don't know. And if one looks throughout the history of our country and other free countries, it is the latter category that tend to be the difficult ones”. The ethical discussion to follow will use Rumsfeld’s definitions. It is our intention to use current scientific literature to evaluate the known knowns and the known unknowns and then to try to speculate on the possible nature of the unknown unknowns. The CRISPR–Cas9 system is easy to use, widely adopted, relatively inexpensive and effective. The relative ease allows for precise changes of genomes and related transcription processes. This enables performing experiments that were considered to be hard or even impossible. Possible uses of CRISPR–Cas9 include replication of genetic basis for human diseases in model organisms, alteration of epigenetic signatures and correction of genetic defects in whole animals as well as in stem cell tissue cultures. Those may lead to new understanding of enigmatic disorders and the creation of new treatments for diseases. (Doudna , Dec 2015) CRISPR promises to provide access to personalized medicine, human genetic modification and the development of new drugs ( Sanders;Akst ) , but with great power comes great responsibility. The Known Knowns Unlike some past examples of genetic engineering, CRISPR- CaS9 is “widely available and relatively simple to employ, and it just lowers the barrier for people to start doing experiments that in the past would have been so difficult to do that there was no reason to discuss regulating them – they were just not very practical.” (Sanders). This calls for urgent regulation efforts that have to be employed at much greater speed than those of past biological innovations.
  • 50. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Although there are existing ethical treatises, regulatory processes are only in preliminary processes and may vary between countries. Because of this, some scientists may be performing experiments the international community may deem as unethical if and when clear guidelines will be formed. A recent example of this are the experiments that done by Chinese scientists on human-embryo editing and the followed discomfort by scientists from other countries (Doudna , Dec 2015). Another debate is regarding whether this technology should be used only to cure diseases and defected genes or also to re- engineer humans to perform better or simply to look better (Brice). It’s not hard to imagine parents wanting stronger, smarter, taller children with blue eyes, for example, who might be tempted by such technology. This raises two issues; eugenics, which has mainly social implications, and the fact that we don’t have a full understanding of the human genome operational process - this will be discussed shortly in the following section. The Known Unknowns “ At least one thing is clear at this stage — we do not yet know enough about the capabilities and limits of the new technologies, especially when it comes to creating heritable mutations.” (Doudna , Dec 2015) CRISPR-CaS9 can be used to genetically engineer germline cells which affects future generations and makes it hard to evaluate the magnitude of influence since the change will not be limited to just one individual but to a large number of individuals (Doudna , Dec 2015). The implications may include off-target alterations and undesired on-target effects. It seems that here the risk of gene editing in human germ cells is too great for us to proceed (Doudna et al.). Experiments with gene editing on insects that aim for the extinction of a whole species are already approved in malaria infected mosquitoes. This may have unknown effects on the ecosystem but the possible benefits of containing malaria seem to outweigh the risks, at least from the perspective of the scientific community and policy makers. The opinions concerning the engineering of human germline cells span from the support of rapid development of the technology to completely banning it. As mentioned in (Doudna
  • 51. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 , Dec 2015) by Dr. Doudna, attempts of bringing the developments to a halt are impractical due to its spread and ease-of-use. Also, it may stop research that will lead to cures of diseases. So, an approach that includes some compromise of the two extremes must be taken. (Doudna et al.) The Unknown Unknowns In a letter to president Roosevelt on 8.2.39, Albert Einstein described the possibility of an atomic bomb being created: “This new phenomenon [chain reaction] would also lead to the construction of bombs, and it is conceivable -- though much less certain -- that extremely powerful bombs of a new type may thus be constructed. A single bomb of this type, carried by boat and exploded in a port, might very well destroy the whole port together with some of the surrounding territory. However, such bombs might very well prove to be too heavy for transportation by air.” As we know by now, atomic bombs are commonly carried by airplanes and they have the power to destroy cities, not just their sea ports. Additionally, hydrogen bombs, which are a direct result of the continued work on the atomic bomb, have even bigger destructive capabilities. This demonstrates the lack of possibility to foresee the outcomes of one’s work even if you are considered to be one the greatest geniuses to ever walk the surface of planet earth. It seems that the international community is committed to the evaluation and prevention of present and future risks arising from CRISPR. As mentioned in (Doudna , Dec 2015), there was a summit in December 2015 that involved scientific delegations from all over the world with the purpose of discussing potential implications and applications of CRISPR- CaS9.(Doudna et al.) So it would appear there was and hopefully still is an ongoing effort to map the unknown. In this section, it seems that just prudent guesses may apply. Here are our humble guesses as to the places where the unknown unknowns would have the largest influence: 1. If international oversight were to stop, or simply be ineffective for political reasons or just because of lack of interest of the community and fail to reach labs who use this technology, no matter where they are in the world.
  • 52. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 2. Secret science experiments sometimes take place in the security/defense industry or in industrial companies . Such a research may be unreported and as a result unregulated. Alternatively, some regulation may just not apply to top secret security research. 3. If certain countries are not a part of the international scientific community, their policy makers are bound to be uninformed regarding the grave implications of this technology. 4. Illegal research may also try to use this technology. For example, gene editing to improve the performance of athletes. It seems to us that the way to overcome these problems is through education. The same way that every child knows about the atomic bomb, every child should know about the possible implications (and advantages) of CRISPR-CaS9. This should provide some measure of defense against negative outcomes as children grow to become scientists and policy makers. Lastly, it is of vital importance to teach ethics as part of molecular biology courses in the university. To conclude this part, the practical steps offered by Dr. Doudna to address some of the issues raised above are (Doudna , Dec 2015): 1. Creation of standards for qualitative measurements of efficiency and off-target effects for genome editing. 2. Creation of professional forums of experts from the fields of genome editing and bioethics. Those will provide a channel for sharing information with the public. 3. Policymakers and scientists from all over the world should cooperate to create clear guidelines as to what is considered to be unethical or ethical research. 4. Effective oversight that will enforce measures of desired efficacy and specificity to the lab work with gene editing on human germ lines. This will be based on the guidelines. 5. Lastly, “human-germline editing for the purposes of creating genome-modified humans should not proceed at this time”. This is because current understanding of human genome does not allow for such a process to take place in a safe manner.
  • 53. Proceedings of the Trans-Disciplinary Innovation Program (TIP) 2016 Conclusion In this review, we have discussed the breakthrough genetic engineering technology of CRISPR-Cas9. This technology has many applications today from knocking in or out genes for basic research, to genetically modifying human cells for elimination of genetic diseases. This technology has the potential to eliminate viral pathogens, create better crops and cure humans of genetic disease. However, there are ethical concerns that arise concerning use of this technology, particularly in the field of human enhancement. Regulations will need to be put in order so to define what this technology can be used for. As of today, we have yet to completely understand the human genome, so while there is great hope in the future of this technology, we must be aware of the great responsibility that lies in the hands of anyone who uses it, and set clear guidelines concerning the ethical use of CRISPR. References Ann Ran, Patrick D Hsu, Jason Wright, Vineeta Agarwala, David A Scott & Feng Zhang (2013). Genome engineering using the CRISPR-Cas9 system. Nature Protocols Vol 9, no.11 , pp. 2281– 2308 Callaway (2016). Second Chinese team reports gene editing in human embryos. Nature News Collins F (2015) Statement on NIH funding of research using gene-editing technologies in human embryos. The NIH Director - National Institutes of Health (NIH). Entine Jon (2015) Ethical and regulatory reflections on CRISPR gene editing revolution. Genetic Literacy Project. Freedman et al (2015). Modelling kidney disease with CRISPR- mutant kidney organoids derived from human pluripotent epiblast spheroids. Nature Communications 6,Article number: 871 Gantz VM, Jasinskiene N, Tatarenkova O, et al (2015). Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. PNAS 112(49):E6736-E6743. doi:10.1073/pnas.1521077112. Ishi T (2015) Germline genome editing in clinics: the approaches, objectives and global society. Brief Funct Genomics: pii: elv053.
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