The Review : We have prepared a classical review on scientific reports about Synthetic Biology and its ethical consequences. With more thant 30 references, you will get a complete overview of the present status of this new emerging field. Ideas of well-known scientist about different topics are gathered here: Definition of SB, The engineering principles of the field, Applications, new chemically different biomolecules, ethical problems with genetic engineering, Europe and USA and teaching and learning SB.

1. THE REVIEW Synthetic Biology...
is a research field tha
t
In the following pages you will find a review about what combines the investig
biology with the cons ative nature of
has been written in specialized journals about Synthetic tructive nature of engin
eering.
Biology and all its ethical implications. Purnick PE, Weiss R.[6]
What was and is Synthetic Biology? Bottom-Up
Nowadays the term Synthetic Biology is widely used in approaches[3], [4]. The Top-Down approach focuses on
the scientific community, but its definition and goals designing and creating working biological devices and,
differ among scientists. The French chemist Stéphane to do so, it aims to create a minimal genome (a
Leduc was the first to use the term in 1912[1], he was “chassis”) and the standardization of parts of DNA with
thinking of creating life from inanimate matter and known function (to make it easier to assemble them).
although some might agree (one century later) that this is The Bottom-Up approach tries to understand evolution
one of the main goals of the field, there is certainly much and the origin of life by creating it from inanimate matter,
more to SB than this. which is why protocells are so important in this new
field. But, is Synthetic Biology a new field?
For a more recent quotation of the term, we have to go
back to 1978, when Szybalski and Skalka extended its Applying Engineering to Biology is not new and, in fact,
meaning, bringing it closer to what SB is considered as Synthetic Biology has a lot in common with other
today: branches of science. According to David Deamer[5], both
Systems Biology and Synthetic Biology have two
“The work on restriction nucleases not only
permits us easily to construct recombinant DNA common theoretical questions to answer: How did life
molecules and to analyze individual genes, but begin? and Can a lab version of cellular life be made?
also has led us into the new era of ‘Synthetic For other experts in the field, SB is just an approach to
Biology’ where not only existing genes are genetic engineering that tries to make it easier and
described and analyzed but also new gene cheaper to genetically modify organisms and can be
arrangements can be constructed and evaluated.” viewed as an extension of genetic engineering.
Szybalski, W. & Skalka, A.[2] Anyway, it seems that the time for a change of paradigm
has arrived. The study of biology has traditionally
Nowadays, experts usually agree that there are at least
focused on a reductionist way of thinking, where
two main ways to look at SB, the Top-Down and the
information about single genes and proteins was
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2. gathered with no
perspective of the 5 categories of
whole cell system.
Synthetic Biology
Synthetic Biology:
and other related Top-Down
Bioengineering Turning biotechnology into a true engineering discipline.
disciplines attempt approach
to turn biologists’ Synthetic genomics Creating of organisms with a chemically synthesized genome.
minds in this new
direction. Unnatural Creating new kind of molecules chemically simillar to the ones
molecular biology existing in order to replace them (XNA, different genetic code).
Re-engineering Bottom-Up
biology Protocells Constructing artificial cells in vitro. approach
It is very common
In silico approaches Informatic simulation and modelling of the other 4 categories.
to hear this
concept when Deplazes, A. [8]
someone tries to define Synthetic Biology, but, what
kind of engineering principles are being considered? Are
these principles in concordance with the complexity of
living matter?
In 2005 Drew Endy wrote a famous article “In an ideal world, desig
ning living systems for
entitled “Foundations for engineering biology” [7] practical purpose should a
be like redesigning a ca
to make it more effi r
where he tried to explain the engineering cient, or redesigning
computer with a faster pro a
principles that need to be applied to Biology: cessor. One would have
the parts, the right softw
Standardization, Decoupling and Abstraction. are, the brains and the
knowledge about the tar
get system, and ‘voilà!’ a
Standards are necessary if we want to design new bacteria that produ
ces
and construct things more easily. We do not need CO2 and light has been cre ethanol from water,
ated.”
to design every nut and bolt of our genetically
modified organism, instead we only have to take the Serrano, L.[9]
7

3. THE REVIEW Synthetic Biology...
of new biological pa
is the design and cons
truction
standardized parts we are going to use and combine rts, devices and syste
and the re-design of ms,
them, knowing they are going to fit without difficulty. The existing, natural biolog
useful purposes. (http ical systems for
Registry of Standard Biological Parts was created by the ://www.syntheticbiol
ogy.org)
MIT as a place where anyone can find a characterized
DNA part that can be mixed and matched to
build synthetic biological devices and And what do biologists think about all
systems [10]. this? They have been studying the
Decoupling means the division of the different molecular complexity of living
simple tasks of a problem. The separation of organisms for more than fifty years and
design and manufacture is a characteristic of some of them are not so convinced by
engineering disciplines. t h e i d e a . G e n e s a re o f t e n n o t
interchangeable among organisms and
Finally, abstraction is important in order to The pillars of synthetic biology.[14] when they are, there is no guarantee
deal with the complexity of living organisms. that their function remains as it was in a
The use of abstraction hierarchies in the flow of genetic different context. What is more, if we know so little about
information enables engineers to work on just one part even the simplest organism known, how are we going to
of the hierarchy without regard for the details of the design a new one?[8]. Organisms replicate and evolve
others. These biological hierarchies have been and this will certainly affect the stability of any designed
compared to the ones found in computer engineering, system in the long-term. Although an effective solution
an interesting analogy made in a recent report[11]. to this particular problem has yet to be discovered, this
Of course, the in silico approach is present in every is not a problem specific to Synthetic Biology[12].
aspect of the field and permits computer modeling and Computer modeling of cell behavior is discussed in
design. Other works also remark the importance of the Goethe's dream [13] and discrete and stochastic
predictability and reliability of the system. As cells mutate approaches have been proposed as much more suitable
and die, these two parameters should be achieved by tools than ordinary differential, traditionally and more
either the use of a large number of cells or by commonly used equations.
synchronization through cell-communication [11].
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4. Applications of Synthetic Biology
Synthetic Biology
Which have been the highlights of Synthetic Biology? 4 areas of research in
What new applications has this field made possible? Are Design and redesign of cellular networks.
these new applications really new?
Genetic circuit engineering.
One of the best known applications of SB is the
production of artemisinin, a drug against malaria that Synthesis of biomaterials.
only the plant Artemisia annua can make, by a
genetically modified organism. In 2006, Dae-Kyun Ro Quest for the minimal organism.
managed to genetically engineer yeasts to produce the Fu, P.[21]
precursor of artemisinin [15] reducing the cost of
cultivating the plants to obtain the drug. But is this
amazing achievement really an application of Synthetic Most of the research on Synthetic Biology has focused
Biology? This particular work is far from the engineering on designing this kind of device, but it is not hard to
principles discussed above, like standardization. Parts realize that although these are incredibly interesting they
taken from different organisms were far from being have little practical application (unlike the work of Dae-
"plugged and played"[16] and this case is not an Kyun Ro with artemisinin). They are, instead, basic
exception. One may think that in the future, as the science, which might be the basis for tomorrow's real
discipline grows, standardization and other engineering synthetic biological applications.
principles will become more and more common, A new chemistry for a new biology
revealing, without any doubt, a challenging scenario for
Several attempts have been made to synthesize new
the development of new biotechnology.
molecules able to substitute those found in organisms.
Designing artificial networks has also yielded some very In this chapter, we will describe such research and
interesting results like switches[17], [18], which are devices discuss its ethical implications as well.
that allow the cell to adopt one of two possible states;
Instead of using DNA or RNA as information-carrying
oscillators[19] which produce regular fluctuations in the
molecules, Piet Herdewijn and Philippe Marlière[22] have
part of networks that allow different cells to
designed new nucleic acids differing only in the sugar
communicate and synchronize between each other[20].
present in the backbone of the structure, that is, instead
9

5. THE REVIEW Synthetic Biology...
aims at making the pr
design and constructi ocess of
of having ribose or deoxyribose, these new models have on of many-componen
engineered biologica t,
threose (TNA), glycerol (GNA), hexitol (HNA) or l systems easier.
cyclohexenyl (CeNA). These new structures do not Shetty RP, Endy D, Kn
ight TF Jr.[25]
essentially differ from the double helix described by
Watson & Crick[23].
This new approach could prevent contamination first sight, does not differ from the ethical questions
between genetically modified and natural organisms as discussed more than thirty years ago when the first
their genetic information would not be compatible. This recombinant DNA techniques were born. So, what's
would make biological devices safer. different now?
The minimal genome project[24] poses new ethical
questions, which need to be discussed. The
creation of a brand-new organism with the only
purpose of using them as a chassis for further
genetic implementation has very different ethical
implications than the idea of modifying naturally
occurring organisms. In the latter case, Synthetic
Biologists would be creating new life forms
instead of modifying them and this is indeed an
entirely new way of looking at nature. The ability DNA
to create life will certainly lead us to a discussion
on the definition of life.
From Asilomar to Synthetic Biology
Ethical questions in Synthetic Biology mostly
focus on risks, paying special attention to the
need of controlling self-replicating machines that
could genetically pollute the environment. This, at RNA
Piet Herdewijn and Philippe Marlière[22]
10

6. In 1975, Paul Berg organized a conference to propose weaknesses into our designed organisms) is not as
an ethical code for genetically engineering living important as intentional harm. Nevertheless, using
organisms in Asilomar, California. The chance to obtain Synthetic Biology for the purposes of Bio-Terrorism is, at
genetic hybrid between an Escherichia coli (a bacterium) least currently, impractical since it is easier and cheaper
and SV40 (a virus that can produce cancer in monkeys) to manage other tools like chemicals or natural non-
raised the alarm of new potential bio-risks (for more engineered organisms[28].
information you can check: Summary Statement of the
Scientists’ actions may also be driven by their dedication
Asilomar Conference on Recombinant DNA
to their work and publications, as Antoine Danchin
Molecules[26]). Certain principles and ground rules for the
comments in the fascinating paper 'Not every truth is
emerging field were announced, but as years passed,
good'[29]. He recounts how the smallpox virus, which
experts started to realize that the technique was not as
only affects humans, was sequenced instead of being
powerful as first thought. Today all the considerations
totally destroyed when it was possible. Now, due to that
discussed at the conference have become obsolete.
negligence, its sequence is freely available on the Web
However, Synthetic Biology, which is a more effective
and thanks to the new, and increasingly cheaper, DNA-
way to engineer organisms, may need new regulations
synthesis techniques, it is an even greater threat than
as strict as those proposed in Asilomar in 1975.
ever. In fact, proposals to regulate the DNA-synthesis
Although designing and creating new biological industry have been made by experts[31], their plan
machines have become much easier and cheaper with serving three purposes: Promoting biological safety and
the rise of Synthetic Biology, this scenario can also
have negative consequences. For instance, the
possibility of non-biotechnologists entering the field “SB's vocabuary identifie
s organisms wiht artifa
and starting to make their own experiments is an identification that, given cts, an
the connection between
evident bio-safety risk. New concepts like bio-hackery 'value', may in the (very) 'life' and
long run lead to a weak
(designing and manufacturing biological systems society's respect for hig ening of
her forms of life that are
without any kind of regulatory oversight) or Do-It- regarded as worthy of pro usually
tection.”
Yourself biology should be closely watched [27].
Experts usually agree that the risk of accidental harm Boldt, J. & Müller, O.[30]
(which can easily be prevented by introducing
11

7. THE REVIEW Synthetic Biology...
involves the creation
ar tificial gene and me of
program new cell an tabolic networks to
d organism behaviors.
Gerchman Y, Weiss [33]
R.
security, encouraging the further development of
synthetic biological technologies and the wide-world Different worlds
application of these regulations. Europe and America are, in fact, two very different
Many groups are now working on establishing some places to practice Synthetic Biology. Just a quick
ground rules for the practice of Synthetic Biology as a comparison shows us that 64% of the publications in
central initiative, like Synbiosafe in Europe, SynBERC in the field came from US laboratories[8]. The European
the USA, or the BBSRC (Biotechnology and Biological Union has already started some initiatives to change this
Sciences Research Council) in the UK. We are at the situation by creating a regulatory and scientific
beginning of a new field and now the right moment infrastructure to support research in this direction, but as
seems to have come to start considering all these Mark Greener[32] points out: "they need to avoid an
ethical and risk-related issues seriously. overly restrictive framework that stifles research".
‘Synbiosafe. Synthetic Biology and its safety and ethical aspects’ is a documentary film
where a lot of experts (including Drew Endy, George Church, Gautam Mukunda or Victor
de Lorenzo) are interviewed by Markus Schmidt and express their opinions in all the topics
related to Synthetic Biology. http://www.synbiosafe.eu/DVD/Synbiosafe.html
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8. Excuse me, where can I learn helping to enlarge the Registry of
some SB? Standard Biological Parts,
Synthetic Biology, like every new field in adding new and characterized
science, is hard to teach and to learn in the gene sequences to the biobrick
usual way for two basic reasons. First, it is database.
hard to define the subject of study
because it is being constantly reanalyzed
and redefined. And second, the interdisciplinary
nature of the field makes it hard to gather and teach to
REFERENCES:
two different kinds of students (basically biologists and
engineers) that have such different backgrounds. Instead
of typical instruction, Natalie Kuldell[34] describes the
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This would include (but not be limited to) the following: France: Poinat.
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9. THE REVIEW Synthetic Biology...
is a ‘field in the makin
combines the experti g’ that
se and knowledge of
biologists and enginee
rs.
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