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Valencia iGEM Team 2009

S i Y s N T tH iE sT In C B I O L O G Y
S n , e h c          a d
                  a comprehensive approach
This book is dedicated to our friends and family.
Thank you for supporting us during these crazy months!
Carles Palanca      Guillem Marco      Miguel Pitarch

                                       Eduardo Otero
Juny Crespo         Sara Rivera
                                       Juli Peretó
Cristina Vilanova   Ángeles Hueso
                                       Arnau Montagud

Manuel Porcar       Jerzy Szablowski   Emilio Navarro
SINS, ETHICS AND BIOLOGY
    Synthetic Biology is a revolutionary scientific discipline.      a comprehensive approach
    The ability to design and construct new biological
    systems with useful properties opens up a challenging
    scenario for the technological development of humanity.
    However, new science needs new regulations, and
    Human Practices dealing with Synthetic Biology must
    be defined in order to provide an ethical, legal and
    regulatory framework within which this novel scientific
    area can develop.
    Sins, Ethics and Biology, a Comprehensive Approach,
    is more than just a review on Human Practices and
    Synthetic Biology: it encompasses a classical review of
    scientific reports on HP; the first comparative analysis
    of previous iGEM HP projects; interviews with well-
    known experts; and the largest survey on ethics and
    Synthetic Biology ever made.
    The goal of this book is to help researchers and people
    interested in SB to assess the new risks, possibilities,
    and ethical issues of this discipline. We hope you will
    enjoy reading it as much as we enjoyed putting it
    together!  


                                          The Valencia Team




4
INTRODUCTION




THE REVIEW     HP: 2005-2008      THE SURVEY      THE EXPERTS
      Page 6           Page 16          Page 28         Page 52




                                                              5
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



6
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
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].




8
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
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
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
THE REVIEW
security, encouraging the further development of
                                                            Synthetic Biology...
                                                                                           involves the creation
                                                                       ar tificial gene and me                    of
                                                             program new cell an               tabolic networks to
synthetic biological technologies and the wide-world                               d organism behaviors.
application of these regulations.
                                                                                                 Gerchman Y, Weiss [33]
                                                                                                                    R.
Many groups are now working on establishing some
ground rules for the practice of Synthetic Biology as a
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".
Different worlds                                              Excuse me, where can I learn some SB?
Europe and America are, in fact, two very different           Synthetic Biology, like every new field in science, is hard
places to practice Synthetic Biology. Just a quick            to teach and to learn in the usual way for two basic
comparison shows us that 64% of the publications in




                          ‘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



12
reasons. First, it is 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 two
                different kinds of students (basically

                                                                                   REFERENCES:
                biologists and engineers) that have such
               different backgrounds. Instead of typical
instruction, Natalie Kuldell[34] describes the possible core
structure of studies in Synthetic Biology. This would               [1]: Leduc, S., (1912) La Biologie Synthétique. Paris,
include (but not be limited to) the following: 1. Students                                                France: Poinat.
will design biological systems in skillful and responsible
ways; 2. Students will design, specify and whenever               [2]: Szybalski, W., Skalka, A., (1978) Nobel prizes and
possible implement their design; 3. Students will                                 restriction enzymes. Gene. 4, 181-182.
conscientiously use materials and 4. Students will define              [3]: de Lorenzo V., Serrano L., Valencia A., (2006)
the values, culture, safety practices, and organizational        Synthetic biology: challenges ahead. Bioinformatics. 22
community of the field.                                                                                     (2), 127–128.
The iGEM is also aimed at young undergraduate                        [4]: Pereto J., Catala J., (2007) The Renaissance of
students who want to know more about Synthetic                      synthetic biology. Biological Theory. 2 (2), 128–130.
Biology. In the summer months, they propose and
design a project that will be presented in early
November. This is a great first step for people who
lack the opportunity to study this subject at their own      More information on socia
                                                                                        l aspects of Synthetic Bio
universities. As they present their project, they are also     can be found in a special                           logy
                                                                                           Issue (guest Edited by M.
helping to enlarge the Registry of Standard Biological       Schmidt) recently publishe
                                                                                          d at Systems and Syntheti
Parts, adding new and characterized gene sequences         Biology (http://www.sprin                                 c
                                                                                      gerlink.com/content/1872
                                                                                                                 -5325).
to the biobrick database.



                                                                                                                      13
THE REVIEW                                                      Synthetic Biology...
                                                                                              is a ‘field in the makin
                                                                              combines the experti                    g’ that
                                                                                                   se and knowledge of
                                                                  biologists and enginee
                                                                                         rs.
                                                                                                          Calvert J, Mar tin P.[35]


  [5]: Deamer D., (2009) On the origin         biology: new                               (2006) Production of the antimalarial
         of systems. Systems biology,           engineering rules for an emerging            drug precursor artemisinic acid in
    synthetic biology and the origin of                discipline. Mol Syst Biol. 2.            engineered yeast. Nature. 440
                 life.. EMBO Rep.. 10.                                                                       (7086), 940-943
                                            [12]: Heinemann M., Panke S., (2006)
[6]: Purnick PE., Weiss R., (2009) The      Synthetic biology: putting engineering       [16]: Karig DK., Simpson ML., (2008)
     second wave of synthetic biology:       into biology.. Bioinformatics.. 22 (22),     Tying new knots in synthetic biology.
    from modules to systems. Nat Rev                                     2790-2799                        HFSP J. 2 (3), 124-8
           Mol Cell Biol. 10, 410–422.
                                             [13]: Moya A., Krasnogor N., Peretó        [17]: Gardner TS., Cantor CR., Collins
 [7]: Endy, D., (2005) Foundations for             J., Latorre A., (2009) Goethe's        JJ., (2000) Construction of a genetic
    engineering biology.. Nature. 438,      dream. Challenges and opportunities                toggle switch in Escherichia coli.
                             449-453.       for synthetic biology. EMBO Rep. 10,                  Nature. 403 (6767), 339-342
                                                                          S28-S32
      [8]: Deplazes, A., (2009) Piecing                                                   [18]: Atkinson MR., Savageau MA.,
   together a puzzle. An exposition of            [14]: de Lorenzo V., Danchin A.,                 Myers JT., Ninfa AJ., (2003)
synthetic biology . EMBO Rep. 10 (2),        (2008) Synthetic biology: discovering           Development of genetic circuitry
                             428-432.         new worlds and new words.. EMBO            exhibiting toogle switch or oscillatory
                                                                 Rep. 9, 822-827                behavior in E. coli. Cell. 13 (5),
       [9]: Serrano, L., (2007) Synthetic
     biology: promises and challenges.        [15]: Ro DK., Paradise EM., Ouellet                                      597-607
                  Mol Syst Biol.. 3:158.    M., Fisher KJ., Newman KL., Ndungu           [19]: Elowitz MB., Leibler S., (2000) A
                                             JM., Ho KA., Eachus RA., Ham TS,                   synthetic oscillatory network of
              [10]: http://parts.mit.edu.
                                                Kirby J., Chang MC., Withers ST.,       transcriptional regulators. Nature. 403
   [11]: Andrianantoandro E, Basu S,         Shiba Y., Sarpong R., Keasling JD.,                               (6767), 335-338
 Karig DK, Weiss R., (2006) Synthetic


14
[20]: Bulter T., Lee SG., Wong WW.,              genome. Science. 319 (5867),           [30]: Boldt J., Müllert O., (2008)
      Fung E., Connor MR., Liao JC.,                                 1215-20          Newtons of the leaves of grass. Nat
    (2004) Design of artificial cell-cell                                                    Biotechnol.. 26 (4), 387-389
                                             [25]: Shetty RP., Endy D., Knight TF
      communication using gene and
                                                  Jr., (2008) Engineering BioBrick   [31]: Bügl H, Danner JP, Molinari RJ,
 metabolic networks. Proc Natl Acad
                                               vectors from BioBrick parts. J Biol      Mulligan JT, Park HO, Reichert B,
       Sci U S A. 101 (8), 2299-2304
                                                                          Eng. 2:5       Roth DA, Wagner R, Budowle B,
   [21]: Fu P., (2006) A perspective of                                                  Scripp RM, Smith JA, Steele SJ,
                                             [26]: Berg P., Baltimore D., Brenner
synthetic biology: assembling building                                                    Church G, Endy D., (2007) DNA
                                               S., Roblin RO., Singer MF., (1975)
blocks for novel functions. Biotechnol                                               synthesis and biological security. Nat
                                            Summary statement of the Asilomar
                     J.. 1 (6), 690-699                                                       Biotechnol. 25 (6), 627-629
                                                conference on recombinant DNA
  [22]: Herdewijn P, Marlière P., (2009)      molecules. Proc Natl Acad Sci U S       [32]: Greener M., (2008) Is the grass
      Toward safe genetically modified                       A.. 72 (6), 1981-1984               greener on the other side?
      organisms through the chemical                                                      Encouraging the development of
                                           [27]: Schmidt, M., (2008) Difussion of
 diversification of nucleic acids. Chem                                               synthetic biology in Europe. Gene. 4,
                                                Synthetic Biology: a challenge to
              Biodivers. 6 (6), 791-808                                                                            181-182
                                                    biosafety. Syst Synth Biol.. 2
  [23]: Watson JD., Crick FH., (1953)                                                 [33]: Gerchman Y., Weiss R., (2004)
                                                [28]: Russ ZN., (2008) Synthetic
Molecular structure of nucleic acids; a                                                Teaching bacteria a new language.
                                                   biology: enormous possibility,
     structure for deoxyribose nucleic                                                 Proc Natl Acad Sci U S A. 101 (8),
                                              exaggerated perils. J Biol Eng.. 4,
   acid. Nature. 171 (4356), 737-738                                                                          2221-2222
                                                                       181-182
       [24]: Gibson DG, Benders GA,                                                      [34]: Kuldell N., (2007) Authentic
                                           [28]: Szybalski, W., Skalka, A., (1978)
Andrews-Pfannkoch C, Denisova EA,                                                           teaching and learning through
                                           Nobel prizes and restriction enzymes.
 Baden-Tillson H, Zaveri J, Stockwell                                                   synthetic biology.. J Biol Eng.. 1:8
                                                                        Gene. 2:7
 TB, Brownley A, Thomas DW, Algire
                                                                                     [35]: Calvert J., Martin P., (2009) The
 MA, Merryman C, Young L, Noskov              [29]: Danchin A., (2002) Not every
                                                                                       role of social scientists in synthetic
  VN, Glass JI, Venter JC, Hutchison                truth is good. The dangers of
                                                                                     biology. Science & Society Series on
CA 3rd, Smith HO., (2008) Complete         publishing knowledge about potential
                                                                                     Convergence Research. EMBO Rep.
  chemical synthesis, assembly, and               bioweapons. EMBO Rep. 3(2),
                                                                                                            10 (3), 201-204
 cloning of a Mycoplasma genitalium                                      102-104


                                                                                                                         15
HUMAN PRACTICES
In this iGEM 2009 edition, we have decided to review
all the information that other teams have written
previously on Human Practices and Synthetic Biology.
We have read and gathered almost thirty reports from
more than twenty teams, between 2005 and 2008, and
classified these texts into four main topics: Synthetic
Biology & iGEM, Biosafety & Risks, Patents and Ethics.




                                                         200
                                                               5 -
                                                                   200
                                                                       8



16
IGEM 2005-2008
Synthetic Biology and the iGEM competition were                     is democratically necessary
recurrent topics in all the Wikis and Human Practices                    for ethical decision-
reports. A lot of groups tried to define and contextualize                making. That's why they
Synthetic Biology, the iGEM and the reasons for their                    prepared a basic survey
participation in the competition.                                         for 100 non-scientists to
                                                                          find out their level of
Definitions of Synthetic Biology are diverse, but the
                                                                             scientific knowledge; what is more they
engineering vision of Biology and the interdisciplinary
character of the field are common ideas present in all of     Phips The Phage addressed a part of their Wiki to this kind of
them. Only the KuLeuven 2008 team has historically           (Heidelberg 08) public, where a funny character (Phips the
                                                                              Phage) guided and explained the project.
contextualized SB as "a logical step in the development
                                                              Calgary 2008 also prepared a survey for adults and
of Biological Science". SB can be classified according to
                                                              high-school students to find out what they knew about
its goals: The main aim of the Bottom-Up approach is to
                                                              SB and the ethical consequences of the field.
create systems from parts while the Top-Down
approach has a much more reductionist vision, which          An explanation about what SB is and how it works, can
tries to encompass a chemical, physical and                  be found in Valencia 2006. Advantages (like the use of
mathematical comprehension of biology (KuLeuven              restriction enzymes or modeling) and disadvantages (like
2008). Among potential applications, biofuels and those      the difficulties of applying engineering to living systems)
related to medicine stand out (Brown 2007, Valencia          as compared to classic genetic engineering are
2006). Synthetic Biology is often overrated and it is easy   discussed. Nevertheless, the text is written for scientists
to find sentences like "SB is one of the most audacious       and people who are not related to the field may have
and controversial scientific ideas of the 21st                trouble understanding it.
century" (KuLeuven 2008) or "This is what I always
                                                             Regarding the iGEM competition, an explanation of its
wanted Biology to be" (Quote from a student, Brown
2007).                                                       history can be found at Berkeley 2008, this extensive
                                                             text starting with the donation of American funds and
Brown and Heidelberg’s teams did a great job of
                                                             ended with the 2008 edition. Likewise, a lot of teams
disseminating SB in their university and informing the
general public about the meaning of this new field.           often refer to the Austin-Texas' Bio-Film but with
Actually, Heidelberg 2008 (Best Human Practices              different intentions: Berkeley brands it as "infamous"
Advance ‘08) justified their work in a sociological tone,     and Brown 2006 as a successful work born in the
arguing that the general public’s knowledge of Science       iGEM.
                                                                                                                       17
HUMAN PRACTICES
Since the beginning of the iGEM competition at an          (KULeuven 2008, Valencia 2008) have continued
international level in 2005, Biosafety concerns have       gathering information and highlighting the key role of
been one of the most widely discussed issues. Like         maintaining sterility on the bench. The idea of lab
most reports on this topic, we will hereafter consider     safety is also supported by focusing on different
Biosafety and Risk as separate terms. Biosafety refers     physical and chemical agents commonly used in
to good practices in the laboratory, whereas Risk is       Molecular Biology: EtBr, UV light (Pavia 2008,
related to the consequences that a genetically modified     Bologna 2008), dry ice, liquid nitrogen (Purdue 2007)
organism could have when released into the                 etc, as well as some warnings about their use or
environment. Certainly both terms are intimately related   storage.
because incorrect lab practices might result in the
                                                           And what about the Risks? Just a few examples to
uncontrolled spreading of genetically engineered
                                                           have been forecasted involve unexpected mutations
microorganisms, which might disturb the ecological
                                                           when a gene is introduced inside an organism
balance.
                                                           (KULeuven 2008), the mixture of natural and artificial
Many teams have indeed taken into account the              gene pools, the unpredictability of synthetic organism
importance of Biosafety in Synthetic Biology, as           proliferation     (Freiburg 2008), and the use of
demonstrated by the “training” that some students          microorganisms                as
have received before starting working on the wetlab        “bioweapons” (Valencia 2008).
(Purdue 2007, Slovenia 2008); the supervision of their     The growth of Risks with the
lab practices by an expert (Zurich 2008, Pavia 2008,       advance of massive sequencing
Slovenia 2008, TUDelft 2008) or university                 techniques, free distribution of
department (Washington 2008); or the establishment         DNA, etc. was discussed by
of different levels of “biological danger” with the        TUDelft 2008 and Freiburg
appropriate security measures (Zurich 2008, Slovenia       2008 teams that also
2008, Edinburgh 2008, Bologna 2008).                       recognized the difficulty of
                                                           building effective barriers, and
One of the main topics discussed in Biosafety is the
                                                           concluded that stopping
importance of working in sterile conditions as stated in
                                                           technical advance is obviously
the first report on Biosafety issues in the iGEM
                                                           not the solution to checking
competition (MIT 2005). Since then, two more teams



18
IGEM 2005-2008
Risks. Finally, a very interesting classification of
different types of risks was proposed by KULeuven in
2008 and different perceptions about risk by TUDelft
2008.
As previously mentioned, Biosafety and Risks are
closely related, so choosing the safest "chassis" for a
Synthetic Biology project is an extremely important
task in terms of Biosafety because of the associated
risks. This is probably the reason why most iGEM
teams implement control strategies for their GM
microorganisms. The most commonly proposed systems to avoid the release and spread
of synthetic microorganisms are: using non-pathogenic bacteria (Edinburgh 2008);
inserting a gene for automatic self-destruction under certain conditions (Freiburg 2008,
Slovenia 2008); replacing an essential gene (KULeuven 2008); using toxin-antitoxin
systems (Valencia 2008) and using lab-specific strains free of toxin- or resistance-
containing plasmids (Pavia 2008).
The importance of improving synthetic circuits and ensuring their safety and suitability to
fulfill their final function been also highlighted (KULeuven 2008, Edinburgh 2008,
Caltech 2008).




                                                                                              19
HUMAN PRACTICES
Since the iGEM 2007 competition, several teams have         ownership of parts already
pointed out the need to examine ethical considerations      present in nature, but a new
on Synthetic Biology related to the open-source             and unique way of putting
character of the technology and its relationship with       them into use for purposes
commercialization of ideas and patent laws. UCSF            other than the original
2008 raised this simple point: do we need patents?          ( Va l e n c i a    2008).
They detailed the advantages and disadvantages of           Furthermore, the
patenting and compared patenting with an alternative:       application must be both
keeping trade secrets (like the Coca Cola formulation).     novel and non-obvious over
                                                            the prior (Berkeley UC
In our society, scientific research on patented
                                                            0207).
applications is possible without licenses. However,
license fees have to be paid when an investigated           Debate about the
application is subsequently commercialized (TUDelft         intellectual property of Parts
2008).                                                      is a very important issue, to which not enough attention
                                                            has been paid (Valencia 2008). But, could a Biobrick-
The iGEM competition ideal is a community sharing
                                                            based device be patented? After outlining the terms of
parts, devices, systems and ideas. BioBricks are the
                                                            the legal OpenWetWare archive, UCSF 2008
best example of this spirit (UCSF 2008). The idea is
                                                            concluded that  open source parts that are further
that BioBricks are added to a database in a completely
                                                            developed should be “patentable” whereas the original
open-source setting. However, the free-market
                                                            parts used must remain open source.
environment, academic and company interests, the
possibility of deliberate misuse (TUDelft 2008),            Aspects such as use, composition and methods should
economic viability and information safety have to be        be included as a claim or a set of claims in the
considered. On the other hand, basic tools and              application. Thus each aspect might be separately
knowledge for the use of these Units should be              patentable. Moreover, the time line for the patent
available to researchers in other areas (Valencia 2008).    application would not start when the part is listed in the
                                                            register. Instead, it would start when the application of
The particular use of different parts (the basic element)
                                                            the part has been publicly disclosed. (Berkeley UC
on integrated systems and devices does not imply
                                                            2007)



20
IGEM 2005-2008
Regarding iGEM projects, a few teams have focused
on the patentability of their projects (UCSF 2008,
Berkeley UC 2007), or made a statement claiming to
have released their research into the public domain
(Edinburgh 2008). However, it has to be noted that if a
company improves the process they have developed, it
could not be prevented from patenting that innovation.
A different and novel approach to this issue was
proposed by Edinburgh 2007, who organized a
presentation on Intellectual Property laws and how
these might apply to Synthetic Biology. This team
highlighted existing similarities between Synthetic
Biology and the Linux-based open source code.
Finally, Berkeley UC 2007 raised three important
questions: the limitations on part and device definitions,
research protocols design, and Synthetic Biology as a
driver for inventing new modes of industrial practices
and partnerships.




                                                            21
HUMAN PRACTICES
The quality of our lives is determined by the quality of     human beings disappeared and left behind a
our thinking. The quality of our thinking, in turn, is       population of Synthetic Biological systems? (Valencia
determined by the quality of our questions. This is          2008).
Linda Elder’s view[1], and it is also ours. In this sense,
                                                             What properties and traits do we want to give to our
many iGEM teams have recently raised interesting
                                                             new organisms? Are there differences between the
bioethical questions. This chapter summarizes all these
                                                             creation of more complex, for instance multi-cellular
questions. And a few answers.
                                                             systems, and organisms? (KULeuven 2008). Bio-
What can we expect from Synthetic Biology?                   engineers even start to cross the thin line between
(KULeuven 2008) Is society ready for this new,               manipulating life and creating life. (Freiburg 2008)
extreme form of genetic engineering? (TUDelft 2008)          When does a natural system become a mechanical
Which practical implementations are possible?                structure? (TUDelft 2008) Do we have to look at
(KULeuven 2008) Should recombinant DNA                       synthetic organisms as just ordinary life forms or should
techniques be the solution to all the world’s problems?      they have the same value as machines? (KULeuven
(TUDelft 2008) Freiburg 2008 and Valencia 2008               2008).
declare that synthetic biological approaches promise to
                                                             How is Synthetic Biology presented in the media, is it
fight some of these problems and KULeuven 08 aims
                                                             just another hype? (TUDelft 2008) What politics are
at proving to the reader that synthetic biology is in fact
                                                             involved and which "societal
a logical step in the continuous development of
                                                             sufferings" are chosen to
Biological Sciences.
                                                             be      remedied?
Are there any new ethical issues related to Synthetic        (UCBerkeley 2008)
Biology? (KULeuven 2008). Under the “banner” or flag          Should science
of Synthetic Biology, should research be allowed so          always depend on
much further than that of genetic modification in             public involvement?
classical bioengineering? (TUDelft 2008). Should the         Scientists can’t
fear to new deleterious biological devices stop scientific    make decisions
development? (Valencia 08). Is it morally acceptable to      without considering
change the nature of life on earth to better suit man’s      the opinion of the common
desire? (KULeuven 2008). What would happen if                people. (KULeuven 2008)



22
IGEM 2005-2008
How does the research being done by the students in        Synthetic Biology. Meanwhile,
the iGEM lab relate to other projects being pursued        TUDelft 2008 stated that ethical
under the banner of Synthetic Biology? What does it        decisions have to be made
mean to be a human practices member of an iGEM             throughout the entire project
team? Doing Synthetic Biology (experimenting,              development.
designing projects, situating findings within it, making
                                                           Finally, Calgary 2008 prepared
decisions about what projects are important, etc.) is a
                                                           two online surveys, one written for high-school
human practice. (UCBerkeley 2008). In its Code,
                                                           students and the other for adults, to better understand
Valencia 2008 exposed three general commitments
                                                           the level of knowledge of Synthetic Biology, what was
regarding bioethics: research on Synthetic Biology must
                                                           forecast about its future, implications and advances
not be directed by economic interests, animal dignity
                                                           and which framework of governance Synthetic Biology
must be assured in every synthetic biology-related
                                                           should have. Valencia 2008 was the first to propose
                  research program and common
                                                           what they called the Concentric Units of Ethical Issues
                       sense should be followed.
                                                           whereas UCBerkeley 2008 enumerated the proposals
                       Moreover, there have been           from SynBERC and used a blog, a notebook and the
                       several discussions among           ArsSynthetica web to follow the development of their
                       terms, as shown in: “ethics of      ethical study.
                       consequences” vs. “ethics of
                                                           And among all these questions, the one that might be
                        principles” (KULeuven
                        2008), “standardized               the ultimate question: Is the world
                        BioBricks” or “standardized        prepared for Synthetic Biology?
                    science” (TUDelft 2008) and            (Calgary 2008).
                 “bottom-up approach” vs. “top-
             down approach” (KULeuven 2008).
Furthermore, KULeuven 2008 also cited the “Three
laws of Robotics” (Isaac Asimov, 1942) and postulated
justice, autonomy and culture as the three central ideas
that are present in all debates concerning ethics and



                                                                                                               23
HUMAN PRACTICES
                                                            In 2008, a “Best Human Practices Advance” was
                                                            recognized for the first time in the iGEM competition as a
                                                            special prize. The Heidelberg team won this award for
                                                            a report on Synthetic Biology and scientific
                                                            communication, in which they discussed the role of the
                                                            media in scientific dissemination as well as people’s
                                                            opinion and knowledge about Synthetic Biology. They

                CONCLUSIONS                                 also included surveys and an interview of a Nobel Prize
                                                            winner.
Human Practices are becoming more and more                  The four topics listed in our review (SB & iGEM,
important in the iGEM competition. In the first              Biosafety & Risks, Patents and Bioethics) have had
international edition, in 2005, only the MIT team wrote a   different relative importance in each iGEM edition.
very brief reference to Biosafety issues in its project.    SB & iGEM was mentioned for the first time in three
However, since then, there has been an exponential          reports in 2006. The number of teams which included
increase in the number of teams dealing with this issue,    this topic in their work was the same in 2007 but
including a Human Practices report.                         increased in 2008 from three to five reports.




24
IGEM 2005-2008
                 Despite being the only topic cited
                 in 2005, Biosafety & Risks was
                 not included in any of the 2006
                 reports and just in one of the 2007
                 edition. However, it has been the
                 most widely discussed issue in
                 2008 (eleven reports) and also in the whole iGEM
                 competition (a total of thirteen).
                 In 2007, two teams introduced a new issue: Patents.
                 The number of reports on intellectual property doubled
                 in the following iGEM edition.
                 The iGEM community had to wait until 2008 to read
                 some reports on another new topic: Bioethics, which
                 became the second most-discussed issue of that year
                 (seven reports).




                                                                   25
HUMAN PRACTICES
The variety of topics included in Human Practices reports has increased every year:




26
IGEM 2005-2008
Furthermore, iGEM teams have tried to make Synthetic
Biology closer to non scientists by including surveys
addressed to the general public (Heidelberg, TUDelft
and Calgary 2008); developing a glossary in which terms
like Synthetic Biology, Systems Biology, Biotechnology,
Metabolic Engineering, System, etc. are defined and
briefly explained (Valencia 2008); or by designing a part
of the Wiki for people without a strong biological
background (Heidelberg 2008).
Finally, one of the funniest points of Human Practices
reports are quotations, often referring to contemporary
science fiction heroes’ ethics, which are used as
metaphors of today’s SB challenges.



                                                                “With great power comes
                                                                                            great responsibility”
                                                                        Spiderman’s uncle Ben (Va
                                                                                                  len    cia 2008)

                                                           “Fear leads to anger. Ange
                                                                                    r leads to hate. Hate leads
                                                                                                   to suffering”
                                                                                Master Yoda (KULeuven
                                                                                                          2008)




                                                  [1] : The Art of Asking Essential Questions. By Linda Elder and
                                             Richard Paul. 48 pages. The Foundation for Critical Thinking. 2006.
                                                                                                                    27
THE SURVEY




28
29
THE SURVEY




30
31
THE SURVEY




32
33
THE SURVEY
With this survey, we wanted to know people’s opinion               who do not know about SB (hereon “informed” vs.
on several topics related to Synthetic Biology. That’s             “uninformed”), and iGEM members vs. non iGEM
why we prepared a short questionnaire which was                    members. Exceptionally, other groups like those
addressed to both iGEM members as well as other                    informed vs. uninformed about the iGEM competition,
people. We tried to write the questions in a clear                 and engineers vs. life scientists will be differentiated in
language, avoiding the use of technical words.                     some questions.
Our survey was available from July 29th to October                 These are the main results of our survey:
12th in our Wiki. We also sent personalized mails to all
                                                                   Question 1. Do you know what Synthetic Biology
2009 iGEM teams inviting them to fill it in, we posted
                                                                   is?
the survey in some important websites such as
www.synbiosafe.eu or www.syntheticbiology.org, and                     A
also in well-known social networks like Facebook.
We got 1288 answers, which made our survey the
biggest one ever made (to the best of our knowledge,
the ¿¿Royal Academy of Engineering?? survey, with
1005 participants, was the biggest one ever made
before). 643 answers came from members of 101
i G E M 2 0 0 9 t e a m s . We a c k n o w l e d g e d t h e i r
collaboration by designing gold (100% of members
                                                                                                               Question 1
have responded), silver (75%) and bronze medals (50%)
for their Wikis (see page 43). The other 645 answers
                                                                   A total of 864 people out of the whole 1288
came from people belonging to many different social
                                                                   participants (67%), asserted they knew what SB is and
groups (for more details you can see page 69 of our
                                                                   gave their own definition (these definitions are analyzed
Appendix).
                                                                   in page 48). Obviously, almost all iGEM members (98%)
Besides considering all the participants’ results in our           were able to define SB, whilst the percentage of non
analysis, different groups of people were also                     iGEM members who knew what SB is was substantially
distinguished: people who know about SB vs. people                 lower 36% (see B).



34
It has to be noted that considering the people who are
             not members of iGEM, the percentage of them who
B            can give a definition of SB was higher (74% vs. 23%)
             when they also knew about this competition. That
             shows the important role iGEM plays in the diffusion of
             this emerging field (see C).
             Finally, the number of life scientists who knew about SB
             was higher (81%) than engineers (60%). Regarding
             people from other fields, less than half (45%) were able
             to define SB (see D).

Question 1




Question 1        D
C




                  Question 1




                                                                  35
THE SURVEY
     A                                                                                                        B




     Question 2                                                                                      Question 2

Question 2. Now, without looking at Wikipedia…               classical Genetic Engineering when they are not clearly
select the 5 words you feel are most closely                 defined. SB can be used for creating transgenics, but so
related to Synthetic Biology                                 too could the other disciplines mentioned above. On the
                                                             other hand, Modeling, Standards or BioBrick specifically
DNA, System, BioBrick, Modelling, Standards and              refer to SB.
Creation are by far the words that people consider
more related to SB, followed by Abstraction, PCR and         It is important to highlight that very few people, even SB
Transgenics (See A).                                         uninformed, propose words like Destruction, Anthrax or
                                                             Infection. This means that currently people don’t
However, there are some differences between SB               immediately associate fear or mistrust with the term
informed and uninformed people: the latter don’t             Synthetic Biology. Furthermore, another difference
recognize BioBrick and Standards as SB-related terms,        between SB informed and uninformed is the following: if
and point out another word: Transgenics. (See B).            answers from life scientists and engineers are
This fact can be due to their incapacity to distinguish SB   compared, there are no significant differences when they
from other similar disciplines such as Biotechnology or      know what SB is, as it is a deeply interdisciplinary
                                                             science; however, when SB is unknown, engineers and



36
C                                C




                                         Question 2                       Question 2

life scientists choose the words more closely related with
their own fields. Words such as PCR, System, Modelling
and Standards are good examples (see C).
Question 3. Knowing that parts of genetic                    A
information can be isolated, do you think these
pieces should be patentable or open source?
Regarding intellectual property, people agree (74%) in
considering that parts of genetic information should be
open source. Only 13% of participants think that they
should be patentable (see A).
Comparing iGEM members and not iGEM members,
there is a difference of opinions. A higher percentage of
iGEM participants (80% vs. 68%) asserted that parts          Question 3
should be open source. This result agrees with the iGEM



                                                                                       37
THE SURVEY
              B      ideals on this topic, for instance, the creation of the
                     Registry of Parts, in which anyone can find lots of free
                     standardized parts (see B).
                     The idea of open source is better supported by SB
                     informed (79%) than by SB uninformed (63%). However,
                     it has to be noted that a significant percentage (22%) of
                     the latter ones did not have a clear opinion (see C).
                     No significant differences were found between life
                     scientists and engineers. However, the percentage of
                     people from other fields who believed that genetic parts
       Question 3
                     should be open source was lower (64% vs. 80% and
                     75%) (see D).




               C                                                    D




        Question 3                                          Question 3




38
Question 4. Let’s assume that humans can create                        B
artificial life. Do we have the right to do it?
The creation of artificial life is a more controversial issue.
Although most people (63%) assert that human beings
have the right to create life in the laboratory, 26% do not
approve. Interestingly, a significant 11% of participants
were unable to give an answer because of the
transcendence and the moral and religious implications
of this topic (see A).
There are no significant differences between iGEM
                                                                Question 4
members and non iGEM members (see B).
But there is a difference on comparing SB informed and
uninformed. The percentage of the latter that agree with
the creation of artificial life is not as high (57%) as the
former (66%) (see C).

                                                    A                  C




                                           Question 4           Question 4




                                                                             39
THE SURVEY
                                                      D                                                        A




                                             Question 4                                                 Question 5

Furthermore, the percentage of life scientists who                Question 6. Do you think there are significant
approve of the creation of artificial life (67%) is slightly       ethical differences between Classic Genetic
higher than the one of engineers (62%) and other fields            Engineering and Synthetic Biology?
(58%) (see D)                                                     On the differences between classic GE and SB, we can
Question 5. Do you think is possible a situation                  conclude that there is a maximum parity between both
such as many science-fiction movies as "I, Robot",                 views. However, 179 people out of        1288 did not
"Terminator", etc, in which humans go a step too                  understand the meaning of the question (see A).
far in their need for improving themselves?
The vast majority of people (97%) who agree with the
creation of artificial life don’t believe that this hypothetical
power could lead us to the irrational situation that many
science-fiction movies show.




40
A                B




                                       Question 6        Question 6

An interesting finding is that iGEM members and non
members have opposite opinions: more than half (52%)
of the iGEM members consider that there are no
significant ethical differences between SB and classic
GE, whilst only the 31% of non iGEM members agree
with that (see B).                                              C
Another finding is that, despite the number of “What?”
responses rate is 22 points higher for those who claim
not to know what synthetic biology is, the “Yes”
percentage has practically remained the same in both
groups (see C).




                                                         Question 6



                                                                      41
THE SURVEY
Question 7. Do you think eating a transgenic               Similarly, there is a difference of 17 percent between SB
vegetable is harmful for your health?                      informed vs. uninformed who assert that eating a
                                                           transgenic vegetable is harmful, which means that
Regarding eating transgenic vegetables, more than 60%
                                                           people knowing about synthetic biology distrust GM
of interviewed people believe that they are not harmful
                                                           food less (see C).
for their health, whilst 362 out of 1288 relate their
response to a particular case of modified food (see A).     The percentage of participants that consider transgenic
                                                           food dangerous changes among fields: Only 5% of life
A surprising result is the high percentage of iGEM
                                                           scientists do not trust these products, whilst the
members and SB informed who chose the third option
                                                           percentage of engineers and people from other fields
(“It depends. I would agree with the Golden Rice, not
                                                           with this opinion is more than twice and four times
with Roundup Ready strains”), as there is no reason for
                                                           higher, respectively (see D).
these vegetables to be more dangerous than other
transgenic products. However, the percentage of iGEM       Question 8. Do you think eating a drug produced in
members that consider transgenic food dangerous is         a genetic modified organism (GMO) is dangerous
slightly lower (5%) than for non iGEM participants (17%)   for your health?
(see B).

                                               A                                                           B




                                        Question 7                                                 Question 7




42
C     Similarly, the majority argues that there is no problem in
             eating a drug produced in a genetically modified
             organism. Interestingly, there is a slightly higher
             percentage (4%) of people against drugs produced in
             GM than against transgenic vegetables (see A).
             The results reveal an increased confidence in GMO
             products (difference of 10%) by those who are iGEM
             participants compared with those who are not (see B).
             The same conclusion can be reached on comparing SB
             informed and uninformed people (see C).
Question 7
             Once again, there is no agreement between people from
             different fields. Drugs produced in GMOs are rejected
             less by life scientists (8%) than by engineers (17%).



        D                                                     A




Question 7                                           Question 8




                                                                   43
THE SURVEY
Participants from other fields distrusting this type of         Disaggregating the responses by groups in each
drugs was higher (28%):                                        ranking, we must point out a clear trend: people with a
                                                               greater awareness of Synthetic Biology believe that it is
Question 9. From 1 (nothing) to 5 (completely) how
                                                               potentially more beneficial and less dangerous than
dangerous or beneficial do you think Synthetic
Biology is?                                                        Question 8
Only 36 out of 1288 think that Synthetic Biology is a little         C
or not beneficial at all. But, on the other hand, more than
82% of the opinions see this new area as highly or
completely beneficial.
Analyzing hazard, we can see that almost 35% have
chosen the more neutral option. But if we study the
more extreme options, 306 responses out of 1288 say
that Synthetic Biology is very or completely dangerous
whilst 42% of interviewees consider it not at all or a bit
hazardous.

                                                    B                                                          D




                                           Question 8                                                 Question 8



44
uninformed people. A similar conclusion can be
obtained when iGEM members and non members are
compared.


                                       A         Beneficial




                                Question 9        Question 9


                                       B         Dangerous




                                Question 9        Question 9




                                                               45
THE SURVEY                                                            Finally we want to th
                                                                                            ank all the iGEM te
Question 10. Do you think we should continue                          that have helped us                          ams
research on Synthetic Biology?                                                             to fill in this survey.
                                                                      designed some m                               We
                                                                                          edals according to
The last question has revealed a virtually total approval             collaboration, they                         their
                                                                                          can post them on
to continue research in Synthetic Biology. Only 19 out of             Wiki if they want.                          their
1288 disagree with the development of this new
discipline.

                                                  B




                                                                Gold (100% of the team members have filled our survey):
                                                                Imperial College London, Paris, Minnesota, Chiba, Harcard,
                                                                SupBiotech-Paris, NTU Singapore, IPN.UNAM Mexico,
                                         Question 10
                                                                Sheffield, Heidelberg, DTU Denmark, KU Leuven, Virginia
     Commonweath, TorontoMaRSDiscovery, UAB Barcelona, Southhampton, Slovenia, SDU Denmark, British Columbia,
     Wisconsin Madison, Edinburgh, Groningen, Freiburg Bioware, Freiburg Software, UCL London, TU Delft, Calgary, LCG-UNAM
     Mexico, UQ Australia, Art Science Bangalore, IT Bombay India, Brown, Berkeley Software, BCCS Bristol.
     Silver (75% of the team members have filled our survey): PKU Beijing, Lethbridge, SJTU Biox Shangai, Upsala Sweden,
     Victoria Australia.
     Bronze (50% of the team members have filled our survey): Cambridge, Missouri Miners, Wash U, Victoria BC, NYMU Taipei,
     EPF Lausanne, Yeshiva NTC, Mo Western Davidson, Virginia U Chicago, Bay Arka RSI, Michigan, Queens, Johns Hopkins
     Bagm Bologna, USTC, Biotec Dresden, USTC Software, IIT Madras, Washington, ULB Brussels, UC Davis.

                                     *643 Members from all iGEM Teams have answered to our survey (58% of the total)



46
CONCLUSIONS
                                                               Other works with a similar goal have been published this
                                                               year[1], [2]. In their surveys, fewer people participated (16
                                                               personally and 1005 interviewed by telephone[1], and
In our opinion, Synthetic Biology is a novel discipline that   1001[2]) and they were only addressed to UK[1] and
is beginning to be well-known among society. The               USA[2]. Synthetic Biology: public dialogue on Synthetic
general public does not seem to be afraid of SB, even          Biology[1] is the first UK’s public dialogue of Synthetic
though it is a revolutionary area. However, a lot of people    Biology that explores people’s views and attitudes
do not have a clear idea of what it is, so more efforts        towards this discipline. It was carried out by The Royal
should be addressed to disseminating this new field.            Academy of Engineering (www.raeng.org.uk). Its
                                                               objectives were to determine public awareness of SB,
Similar answers were found among different groups              explore uninformed and informed public attitudes to SB,
when we asked them about creating life in the laboratory       identify particular hopes, expectations and concerns
and problems regarding intellectual property. We think         relating to the development of the technology, and
that these profound issues are strong convictions              identify issues that merit further research and/or
formed early in life and are hard to change. This              dialogue activity.
contrasts with questions related to transgenics. One can
clearly see how different answers may be in terms of           Finally, Nanotechnology, Synthetic Biology, & Public
participants’ biotechnological knowledge and the field          Opinion[2] is a report of findings based on a survey. It
they are working on. When we asked about ethical               was conducted on behalf of The Woodrow Wilson
differences between Synthetic Biology and classic              International Center for Scholars. This is the fourth year
Genetic Engineering, we also found diverging answers           of the study, but since the second year it included
depending on the social group. According to this               Synthetic Biology. They basically asked about public
information, we may classify ethical questions in two          awareness of SB (with similar results to [1], not a lot of
blocks; when positions are extreme and a debate is             people know about it), the impression of its risks and
usually futile we have “insurmountable issues”, on the         benefits, and concerns about biofuels. Like us, they
other hand, when opinions change depending on                  concluded that there should be more information for the
knowledge of the topic we consider these as “relaxed           general public about new technologies.
issues”.




                                                                                                                        47
THE SURVEY
                        DEFINITIONS
                                                             three of the divisions established. We were not able to
                                                             find any definition that referred to the four criteria.

After considering and comparing all definitions received
(864) they were classified into four different groups.



                             Characteristic
                  SB
                                 concepts.
              and the
             design of
             new systems.

                             Rationalizing
                                 biological
               Engineering    processes.
               approach to
                 biology.



Thus, over 65% of the responses have been included in
one or more of these segments. Obviously, groups are
not mutually exclusive and one definition may fall into
more than one group. However, 66% of the definitions
were classified in a single group, 22% into two main
groups, and only 4% were considered to correspond to




                        You can check all the 863 definitions at http://2009.igem.org/Team:Valencia/All_Definitions
48
In a more detailed analysis, more than half of the answers dealt with the design and creation of new systems
(58%); 48% on the relationship between Synthetic Biology and Engineering; 19% were descriptive definitions
listing some of the basic features of this new discipline such as “standardization” and “abstraction”; and 8%
included the importance of Synthetic Biology in “understanding” biological systems. Words used to define
SB among each of the four groups are listed below.
Synthetic Biology and the design of new systems.
Within this section,
participants have                         tions
defined Synthetic          The best defini
Biology as creation
(38%), designing (33%),        “A new interdisciplinary field that involves the design, construction and
engineering (32%), building    standardization of new biological parts, devices, and systems, and the re-
(14%), modifying (13%),        design of existing, natural biological systems for useful purposes.”
making (8%) and assembling
                                                      Female, undergraduate student, under 20 years old
(2%) new biological systems
(56%), parts (28%),            “Application of engineering principles (modularity, abstraction) to
organisms (18%), devices       rationalize the art of genetic modification, increasing the complexity of
(17%), functions (16%), life   systems that can be designed and constructed reliably.”
forms (12%), components                                             Male, doctoral degree, 31-40 years old
(7%) and machines (4%).
                                 “Synthetic biology is a new discipline of life sciences focused on bringing
Engineering approach to          engineering into biology. It uses engineering concepts like modeling and
Biology.                         standardization to create biological devices with new capabilities that do
                                 not exist in nature.”
This group includes
definitions referring to                                        Male, graduate student – Ph, 21-30 years old
Synthetic Biology as a new
interdisciplinary field where



                                                                                                                49
THE SURVEY
                                                                 Rationalizing biological processes.
                                                                 The last group corresponds to those definitions that
                                                                 consider Synthetic Biology as a field of knowledge that
                                                                 aims to further understand biological systems (70%), the
                                                                 basis of life (18%) and complex biochemical pathways
                                                                 (12%).


                                                                          inal definitions
                                                            The most orig

                                                                 “Engineering + Cell Biology - World Domination.”
                                                                    Male, graduate student – Ph, 21-30 years old
                                                                 “Decouple life, Construct life.”
engineering principles are applied to Biology (69%),             Male, undergraduate student, under 20 years old
Biological Systems (39%), Science (7%), Genetic                   “Synthetic Biology is Systems biology in reverse
Manipulation (6%) and Life Sciences (5%).                        - obtaining in vivo results by in silico prediction.”
Characteristic concepts of Synthetic Biology.                         Male, undergraduate student, 21-30 years old
This group includes definitions which state that Synthetic         “Abstracting biology concepts with an
Biology involves standardization (72%), abstraction               engineering framework to introduce standards
(16%), modularity (14%), modeling (12%),                          into the field. Like lego.”
characterization (5%), interchangeability (3%),
                                                                  Male, undergraduate student, under 20 years old
automation, insulation, transferability, hierarchy,
acceleration and simulation of biological systems (2%).           “Thinking like an engineer and doing like a
                                                                  molecular biologist.”
                                                                          Female, doctoral degree, 31-40 years old



50
using                                                              organisms

       systems
                                construction
                                                                                                          novel
                 existing




  biology     design
                                                        science
                                                                   create


                                                                         genetic                   life
                               devices

    parts                              synthetic new
            functions
                                                                                            natural
Base: All respondants (1288)

  The most repeted words in all of our 863 definitions. Size according to its repetition. “Biology” refers to both “biology and
                                               “biological” terms. This word cloud was created by http://www.wordle.net/


  [1] : Synthetic Biology: public dialogue on synthetic biology. The Royal academy of Engineering. 60 pages. 2009.
            [2]: Awareness of and Attitudes Towards Nanotechnology and Synthetic Biology, Peter D Hart Research
                                Associates. Inc. 17 Pages. Woodrow Wilson International Center for Scholars. 2009.
                                                                                                                       51
THE EXPERTS



      Markus Schmidt                                               Antoine Danchin



Markus Smicht is an Austrian biosafety scientist. His research interests include plant genetic resources,  risk
assessment, public perception, communication, and technology assessment (TA) of novel bio- and nanotechnologies,
including Synthetic Biology. His interest in SB is beyond doubt and he has interviewed many experts in the field (http://
www.synbiosafe.eu/index.php?page=expert-interviews)

With more than three hundred publications in forty years, Antoine Danchin is nowadays, one of the most popular
scientists developing theoretical reflections and experiments in the domain of Synthetic Biology. Trained as a
mathematician and a physicist, his work with Adenylate cyclase is well known, but he has also focused on
Bioinformatics and Philosophy of Science.
Both of them have kindly answered an interview about Synthetic Biology. First, we have asked them to fill in our survey.
If you answered it too, you may be interested in comparing your answers with the ones of our experts. Finally, we have
asked several additional questions on Ethics, Biosafety and the Regulatory frameworks of Synthetic Biology.


52
ANSWERS TO OUR SURVEY
                   Question: Do you know what                Question: Do you know what
                   Synthetic Biology is? Please,             Synthetic Biology is? Please,
                   define it!                                 define it!

                    Answer: Yes, Synthetic biology is the    Answer: Yes,  is the process to
                    design and construction of new           reconstruct life from the chemical
                    biological systems not found in          world.
    Markus          nature. It aims at creating novel                                                    Antoine
                    organisms for practical purposes but
also at gaining insights into living systems by re-
constructing them. SB is an interdisciplinary field,
involving microbiology, genetic engineering, information
technology, nanotechnology, and biochemistry. SB as a
scientific and engineering field includes the following
subfields:
(A) Engineering DNA-based biological circuits, including
but not limited to standardized biological parts;
(B) Defining a minimal genome/minimal life (top-down
approach);
(C) Constructing so-called protocells, i.e. living cells,       As they ar
                                                                             e experts, M
from scratch (bottom-up approach);                             like to foll               arkus and
(D) Creating orthogonal biological systems based on a                       ow the rule                Antoine do
                                                               answers fu               s! They ha                 n’t
biochemistry not found in nature (e.g. non-DNA, non-                         rther than            ve extended
                                                               But since                  requested              their
RNA nucleic acids); and                                                    we think th               in the sur
(E) Gene and Genome DNA synthesis                             valuable, w                eir ideas a             vey.
                                                                           e have inclu              re particula
                                                              read.                      ded them f               rly
                                                                                                    or all of yo
                                                                                                                 u to




                                                                                                                   53
THE EXPERTS
                     Q: Now, without looking at               Q: Now, without looking at
                     Wikipedia, select the 5 words you        Wikipedia, select the 5 words you
                     feel are most closely related to         feel are most closely related to
                     Synthetic Biology. (Answers in bold)     Synthetic Biology. (Answers in bold)

                 A: DNA, Plastic, Destruction,                A: DNA, Plastic, Destruction,
                 Abstraction, Anthrax, System,                Abstraction, Anthrax, System,
     Markus      PCR, Infection, BioBrick,                    PCR, Infection, BioBrick,                Antoine
                 M o d e l l i n g , Tr a n s g e n i c s ,   Modelling, Transgenics, Creation,
       Creation, Standards.                                   Standards.
 
Q: Knowing that parts of the genetic information              Q: Knowing that parts of the genetic information
      can be isolated, do you think these                     can be isolated, do you think these pieces should
      pieces should be ... ?                                  be ... ?
A: Patentable // Open Source // Sorry, I don't                A: Patentable // Open Source // Sorry, I don't know.
      know.                                                   One can only patent the result of inventive activity.
                                                              Therefore isolated genetic information cannot be
Q: Let´s assume that humans can create artificial              patented as such, but only coupled to some kind of
life. Do we have the right to do so?                          inventive activity.
A: Yes // No // Sorry, it's too hard for me.
                                                              Q: Let´s assume that humans can create artificial
Q: Do you think the situation shown in many                   life. Do we have the right to do so?
                        science fiction movies                 A: Yes // No // Sorry, it's too hard for me.
“SB tries to much more is possible, like "I,
                        Robot", "Terminator",                 Q: Do you think the situation shown in many
 rational than Genetic etc, in which humans                   science fiction movies is possible, like "I, Robot",
                        go a step too far in                  "Terminator", etc, in which humans go a step too
     Engeneering.”                                            far in their need for improving themselves?
                        their need for
       (Markus)         improving themselves?



54
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach
Sins, Ethics And Biology - A Comprehensive Approach

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Sins, Ethics And Biology - A Comprehensive Approach

  • 1. Valencia iGEM Team 2009 S i Y s N T tH iE sT In C B I O L O G Y S n , e h c a d a comprehensive approach
  • 2. This book is dedicated to our friends and family. Thank you for supporting us during these crazy months!
  • 3. Carles Palanca Guillem Marco Miguel Pitarch Eduardo Otero Juny Crespo Sara Rivera Juli Peretó Cristina Vilanova Ángeles Hueso Arnau Montagud Manuel Porcar Jerzy Szablowski Emilio Navarro
  • 4. SINS, ETHICS AND BIOLOGY Synthetic Biology is a revolutionary scientific discipline. a comprehensive approach The ability to design and construct new biological systems with useful properties opens up a challenging scenario for the technological development of humanity. However, new science needs new regulations, and Human Practices dealing with Synthetic Biology must be defined in order to provide an ethical, legal and regulatory framework within which this novel scientific area can develop. Sins, Ethics and Biology, a Comprehensive Approach, is more than just a review on Human Practices and Synthetic Biology: it encompasses a classical review of scientific reports on HP; the first comparative analysis of previous iGEM HP projects; interviews with well- known experts; and the largest survey on ethics and Synthetic Biology ever made. The goal of this book is to help researchers and people interested in SB to assess the new risks, possibilities, and ethical issues of this discipline. We hope you will enjoy reading it as much as we enjoyed putting it together!   The Valencia Team 4
  • 5. INTRODUCTION THE REVIEW HP: 2005-2008 THE SURVEY THE EXPERTS Page 6 Page 16 Page 28 Page 52 5
  • 6. 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 6
  • 7. 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
  • 8. 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]. 8
  • 9. 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
  • 10. 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
  • 11. 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
  • 12. THE REVIEW security, encouraging the further development of Synthetic Biology... involves the creation ar tificial gene and me of program new cell an tabolic networks to synthetic biological technologies and the wide-world d organism behaviors. application of these regulations. Gerchman Y, Weiss [33] R. Many groups are now working on establishing some ground rules for the practice of Synthetic Biology as a 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". Different worlds Excuse me, where can I learn some SB? Europe and America are, in fact, two very different Synthetic Biology, like every new field in science, is hard places to practice Synthetic Biology. Just a quick to teach and to learn in the usual way for two basic comparison shows us that 64% of the publications in ‘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 12
  • 13. reasons. First, it is 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 two different kinds of students (basically REFERENCES: biologists and engineers) that have such different backgrounds. Instead of typical instruction, Natalie Kuldell[34] describes the possible core structure of studies in Synthetic Biology. This would [1]: Leduc, S., (1912) La Biologie Synthétique. Paris, include (but not be limited to) the following: 1. Students France: Poinat. will design biological systems in skillful and responsible ways; 2. Students will design, specify and whenever [2]: Szybalski, W., Skalka, A., (1978) Nobel prizes and possible implement their design; 3. Students will restriction enzymes. Gene. 4, 181-182. conscientiously use materials and 4. Students will define [3]: de Lorenzo V., Serrano L., Valencia A., (2006) the values, culture, safety practices, and organizational Synthetic biology: challenges ahead. Bioinformatics. 22 community of the field. (2), 127–128. The iGEM is also aimed at young undergraduate [4]: Pereto J., Catala J., (2007) The Renaissance of students who want to know more about Synthetic synthetic biology. Biological Theory. 2 (2), 128–130. Biology. In the summer months, they propose and design a project that will be presented in early November. This is a great first step for people who lack the opportunity to study this subject at their own More information on socia l aspects of Synthetic Bio universities. As they present their project, they are also can be found in a special logy Issue (guest Edited by M. helping to enlarge the Registry of Standard Biological Schmidt) recently publishe d at Systems and Syntheti Parts, adding new and characterized gene sequences Biology (http://www.sprin c gerlink.com/content/1872 -5325). to the biobrick database. 13
  • 14. THE REVIEW Synthetic Biology... is a ‘field in the makin combines the experti g’ that se and knowledge of biologists and enginee rs. Calvert J, Mar tin P.[35] [5]: Deamer D., (2009) On the origin biology: new (2006) Production of the antimalarial of systems. Systems biology, engineering rules for an emerging drug precursor artemisinic acid in synthetic biology and the origin of discipline. Mol Syst Biol. 2. engineered yeast. Nature. 440 life.. EMBO Rep.. 10. (7086), 940-943 [12]: Heinemann M., Panke S., (2006) [6]: Purnick PE., Weiss R., (2009) The Synthetic biology: putting engineering [16]: Karig DK., Simpson ML., (2008) second wave of synthetic biology: into biology.. Bioinformatics.. 22 (22), Tying new knots in synthetic biology. from modules to systems. Nat Rev 2790-2799 HFSP J. 2 (3), 124-8 Mol Cell Biol. 10, 410–422. [13]: Moya A., Krasnogor N., Peretó [17]: Gardner TS., Cantor CR., Collins [7]: Endy, D., (2005) Foundations for J., Latorre A., (2009) Goethe's JJ., (2000) Construction of a genetic engineering biology.. Nature. 438, dream. Challenges and opportunities toggle switch in Escherichia coli. 449-453. for synthetic biology. EMBO Rep. 10, Nature. 403 (6767), 339-342 S28-S32 [8]: Deplazes, A., (2009) Piecing [18]: Atkinson MR., Savageau MA., together a puzzle. An exposition of [14]: de Lorenzo V., Danchin A., Myers JT., Ninfa AJ., (2003) synthetic biology . EMBO Rep. 10 (2), (2008) Synthetic biology: discovering Development of genetic circuitry 428-432. new worlds and new words.. EMBO exhibiting toogle switch or oscillatory Rep. 9, 822-827 behavior in E. coli. Cell. 13 (5), [9]: Serrano, L., (2007) Synthetic biology: promises and challenges. [15]: Ro DK., Paradise EM., Ouellet 597-607 Mol Syst Biol.. 3:158. M., Fisher KJ., Newman KL., Ndungu [19]: Elowitz MB., Leibler S., (2000) A JM., Ho KA., Eachus RA., Ham TS, synthetic oscillatory network of [10]: http://parts.mit.edu. Kirby J., Chang MC., Withers ST., transcriptional regulators. Nature. 403 [11]: Andrianantoandro E, Basu S, Shiba Y., Sarpong R., Keasling JD., (6767), 335-338 Karig DK, Weiss R., (2006) Synthetic 14
  • 15. [20]: Bulter T., Lee SG., Wong WW., genome. Science. 319 (5867), [30]: Boldt J., Müllert O., (2008) Fung E., Connor MR., Liao JC., 1215-20 Newtons of the leaves of grass. Nat (2004) Design of artificial cell-cell Biotechnol.. 26 (4), 387-389 [25]: Shetty RP., Endy D., Knight TF communication using gene and Jr., (2008) Engineering BioBrick [31]: Bügl H, Danner JP, Molinari RJ, metabolic networks. Proc Natl Acad vectors from BioBrick parts. J Biol Mulligan JT, Park HO, Reichert B, Sci U S A. 101 (8), 2299-2304 Eng. 2:5 Roth DA, Wagner R, Budowle B, [21]: Fu P., (2006) A perspective of Scripp RM, Smith JA, Steele SJ, [26]: Berg P., Baltimore D., Brenner synthetic biology: assembling building Church G, Endy D., (2007) DNA S., Roblin RO., Singer MF., (1975) blocks for novel functions. Biotechnol synthesis and biological security. Nat Summary statement of the Asilomar J.. 1 (6), 690-699 Biotechnol. 25 (6), 627-629 conference on recombinant DNA [22]: Herdewijn P, Marlière P., (2009) molecules. Proc Natl Acad Sci U S [32]: Greener M., (2008) Is the grass Toward safe genetically modified A.. 72 (6), 1981-1984 greener on the other side? organisms through the chemical Encouraging the development of [27]: Schmidt, M., (2008) Difussion of diversification of nucleic acids. Chem synthetic biology in Europe. Gene. 4, Synthetic Biology: a challenge to Biodivers. 6 (6), 791-808 181-182 biosafety. Syst Synth Biol.. 2 [23]: Watson JD., Crick FH., (1953) [33]: Gerchman Y., Weiss R., (2004) [28]: Russ ZN., (2008) Synthetic Molecular structure of nucleic acids; a Teaching bacteria a new language. biology: enormous possibility, structure for deoxyribose nucleic Proc Natl Acad Sci U S A. 101 (8), exaggerated perils. J Biol Eng.. 4, acid. Nature. 171 (4356), 737-738 2221-2222 181-182 [24]: Gibson DG, Benders GA, [34]: Kuldell N., (2007) Authentic [28]: Szybalski, W., Skalka, A., (1978) Andrews-Pfannkoch C, Denisova EA, teaching and learning through Nobel prizes and restriction enzymes. Baden-Tillson H, Zaveri J, Stockwell synthetic biology.. J Biol Eng.. 1:8 Gene. 2:7 TB, Brownley A, Thomas DW, Algire [35]: Calvert J., Martin P., (2009) The MA, Merryman C, Young L, Noskov [29]: Danchin A., (2002) Not every role of social scientists in synthetic VN, Glass JI, Venter JC, Hutchison truth is good. The dangers of biology. Science & Society Series on CA 3rd, Smith HO., (2008) Complete publishing knowledge about potential Convergence Research. EMBO Rep. chemical synthesis, assembly, and bioweapons. EMBO Rep. 3(2), 10 (3), 201-204 cloning of a Mycoplasma genitalium 102-104 15
  • 16. HUMAN PRACTICES In this iGEM 2009 edition, we have decided to review all the information that other teams have written previously on Human Practices and Synthetic Biology. We have read and gathered almost thirty reports from more than twenty teams, between 2005 and 2008, and classified these texts into four main topics: Synthetic Biology & iGEM, Biosafety & Risks, Patents and Ethics. 200 5 - 200 8 16
  • 17. IGEM 2005-2008 Synthetic Biology and the iGEM competition were is democratically necessary recurrent topics in all the Wikis and Human Practices for ethical decision- reports. A lot of groups tried to define and contextualize making. That's why they Synthetic Biology, the iGEM and the reasons for their prepared a basic survey participation in the competition. for 100 non-scientists to find out their level of Definitions of Synthetic Biology are diverse, but the scientific knowledge; what is more they engineering vision of Biology and the interdisciplinary character of the field are common ideas present in all of Phips The Phage addressed a part of their Wiki to this kind of them. Only the KuLeuven 2008 team has historically (Heidelberg 08) public, where a funny character (Phips the Phage) guided and explained the project. contextualized SB as "a logical step in the development Calgary 2008 also prepared a survey for adults and of Biological Science". SB can be classified according to high-school students to find out what they knew about its goals: The main aim of the Bottom-Up approach is to SB and the ethical consequences of the field. create systems from parts while the Top-Down approach has a much more reductionist vision, which An explanation about what SB is and how it works, can tries to encompass a chemical, physical and be found in Valencia 2006. Advantages (like the use of mathematical comprehension of biology (KuLeuven restriction enzymes or modeling) and disadvantages (like 2008). Among potential applications, biofuels and those the difficulties of applying engineering to living systems) related to medicine stand out (Brown 2007, Valencia as compared to classic genetic engineering are 2006). Synthetic Biology is often overrated and it is easy discussed. Nevertheless, the text is written for scientists to find sentences like "SB is one of the most audacious and people who are not related to the field may have and controversial scientific ideas of the 21st trouble understanding it. century" (KuLeuven 2008) or "This is what I always Regarding the iGEM competition, an explanation of its wanted Biology to be" (Quote from a student, Brown 2007). history can be found at Berkeley 2008, this extensive text starting with the donation of American funds and Brown and Heidelberg’s teams did a great job of ended with the 2008 edition. Likewise, a lot of teams disseminating SB in their university and informing the general public about the meaning of this new field. often refer to the Austin-Texas' Bio-Film but with Actually, Heidelberg 2008 (Best Human Practices different intentions: Berkeley brands it as "infamous" Advance ‘08) justified their work in a sociological tone, and Brown 2006 as a successful work born in the arguing that the general public’s knowledge of Science iGEM. 17
  • 18. HUMAN PRACTICES Since the beginning of the iGEM competition at an (KULeuven 2008, Valencia 2008) have continued international level in 2005, Biosafety concerns have gathering information and highlighting the key role of been one of the most widely discussed issues. Like maintaining sterility on the bench. The idea of lab most reports on this topic, we will hereafter consider safety is also supported by focusing on different Biosafety and Risk as separate terms. Biosafety refers physical and chemical agents commonly used in to good practices in the laboratory, whereas Risk is Molecular Biology: EtBr, UV light (Pavia 2008, related to the consequences that a genetically modified Bologna 2008), dry ice, liquid nitrogen (Purdue 2007) organism could have when released into the etc, as well as some warnings about their use or environment. Certainly both terms are intimately related storage. because incorrect lab practices might result in the And what about the Risks? Just a few examples to uncontrolled spreading of genetically engineered have been forecasted involve unexpected mutations microorganisms, which might disturb the ecological when a gene is introduced inside an organism balance. (KULeuven 2008), the mixture of natural and artificial Many teams have indeed taken into account the gene pools, the unpredictability of synthetic organism importance of Biosafety in Synthetic Biology, as proliferation (Freiburg 2008), and the use of demonstrated by the “training” that some students microorganisms as have received before starting working on the wetlab “bioweapons” (Valencia 2008). (Purdue 2007, Slovenia 2008); the supervision of their The growth of Risks with the lab practices by an expert (Zurich 2008, Pavia 2008, advance of massive sequencing Slovenia 2008, TUDelft 2008) or university techniques, free distribution of department (Washington 2008); or the establishment DNA, etc. was discussed by of different levels of “biological danger” with the TUDelft 2008 and Freiburg appropriate security measures (Zurich 2008, Slovenia 2008 teams that also 2008, Edinburgh 2008, Bologna 2008). recognized the difficulty of building effective barriers, and One of the main topics discussed in Biosafety is the concluded that stopping importance of working in sterile conditions as stated in technical advance is obviously the first report on Biosafety issues in the iGEM not the solution to checking competition (MIT 2005). Since then, two more teams 18
  • 19. IGEM 2005-2008 Risks. Finally, a very interesting classification of different types of risks was proposed by KULeuven in 2008 and different perceptions about risk by TUDelft 2008. As previously mentioned, Biosafety and Risks are closely related, so choosing the safest "chassis" for a Synthetic Biology project is an extremely important task in terms of Biosafety because of the associated risks. This is probably the reason why most iGEM teams implement control strategies for their GM microorganisms. The most commonly proposed systems to avoid the release and spread of synthetic microorganisms are: using non-pathogenic bacteria (Edinburgh 2008); inserting a gene for automatic self-destruction under certain conditions (Freiburg 2008, Slovenia 2008); replacing an essential gene (KULeuven 2008); using toxin-antitoxin systems (Valencia 2008) and using lab-specific strains free of toxin- or resistance- containing plasmids (Pavia 2008). The importance of improving synthetic circuits and ensuring their safety and suitability to fulfill their final function been also highlighted (KULeuven 2008, Edinburgh 2008, Caltech 2008). 19
  • 20. HUMAN PRACTICES Since the iGEM 2007 competition, several teams have ownership of parts already pointed out the need to examine ethical considerations present in nature, but a new on Synthetic Biology related to the open-source and unique way of putting character of the technology and its relationship with them into use for purposes commercialization of ideas and patent laws. UCSF other than the original 2008 raised this simple point: do we need patents? ( Va l e n c i a 2008). They detailed the advantages and disadvantages of Furthermore, the patenting and compared patenting with an alternative: application must be both keeping trade secrets (like the Coca Cola formulation). novel and non-obvious over the prior (Berkeley UC In our society, scientific research on patented 0207). applications is possible without licenses. However, license fees have to be paid when an investigated Debate about the application is subsequently commercialized (TUDelft intellectual property of Parts 2008). is a very important issue, to which not enough attention has been paid (Valencia 2008). But, could a Biobrick- The iGEM competition ideal is a community sharing based device be patented? After outlining the terms of parts, devices, systems and ideas. BioBricks are the the legal OpenWetWare archive, UCSF 2008 best example of this spirit (UCSF 2008). The idea is concluded that  open source parts that are further that BioBricks are added to a database in a completely developed should be “patentable” whereas the original open-source setting. However, the free-market parts used must remain open source. environment, academic and company interests, the possibility of deliberate misuse (TUDelft 2008), Aspects such as use, composition and methods should economic viability and information safety have to be be included as a claim or a set of claims in the considered. On the other hand, basic tools and application. Thus each aspect might be separately knowledge for the use of these Units should be patentable. Moreover, the time line for the patent available to researchers in other areas (Valencia 2008). application would not start when the part is listed in the register. Instead, it would start when the application of The particular use of different parts (the basic element) the part has been publicly disclosed. (Berkeley UC on integrated systems and devices does not imply 2007) 20
  • 21. IGEM 2005-2008 Regarding iGEM projects, a few teams have focused on the patentability of their projects (UCSF 2008, Berkeley UC 2007), or made a statement claiming to have released their research into the public domain (Edinburgh 2008). However, it has to be noted that if a company improves the process they have developed, it could not be prevented from patenting that innovation. A different and novel approach to this issue was proposed by Edinburgh 2007, who organized a presentation on Intellectual Property laws and how these might apply to Synthetic Biology. This team highlighted existing similarities between Synthetic Biology and the Linux-based open source code. Finally, Berkeley UC 2007 raised three important questions: the limitations on part and device definitions, research protocols design, and Synthetic Biology as a driver for inventing new modes of industrial practices and partnerships. 21
  • 22. HUMAN PRACTICES The quality of our lives is determined by the quality of human beings disappeared and left behind a our thinking. The quality of our thinking, in turn, is population of Synthetic Biological systems? (Valencia determined by the quality of our questions. This is 2008). Linda Elder’s view[1], and it is also ours. In this sense, What properties and traits do we want to give to our many iGEM teams have recently raised interesting new organisms? Are there differences between the bioethical questions. This chapter summarizes all these creation of more complex, for instance multi-cellular questions. And a few answers. systems, and organisms? (KULeuven 2008). Bio- What can we expect from Synthetic Biology? engineers even start to cross the thin line between (KULeuven 2008) Is society ready for this new, manipulating life and creating life. (Freiburg 2008) extreme form of genetic engineering? (TUDelft 2008) When does a natural system become a mechanical Which practical implementations are possible? structure? (TUDelft 2008) Do we have to look at (KULeuven 2008) Should recombinant DNA synthetic organisms as just ordinary life forms or should techniques be the solution to all the world’s problems? they have the same value as machines? (KULeuven (TUDelft 2008) Freiburg 2008 and Valencia 2008 2008). declare that synthetic biological approaches promise to How is Synthetic Biology presented in the media, is it fight some of these problems and KULeuven 08 aims just another hype? (TUDelft 2008) What politics are at proving to the reader that synthetic biology is in fact involved and which "societal a logical step in the continuous development of sufferings" are chosen to Biological Sciences. be remedied? Are there any new ethical issues related to Synthetic (UCBerkeley 2008) Biology? (KULeuven 2008). Under the “banner” or flag Should science of Synthetic Biology, should research be allowed so always depend on much further than that of genetic modification in public involvement? classical bioengineering? (TUDelft 2008). Should the Scientists can’t fear to new deleterious biological devices stop scientific make decisions development? (Valencia 08). Is it morally acceptable to without considering change the nature of life on earth to better suit man’s the opinion of the common desire? (KULeuven 2008). What would happen if people. (KULeuven 2008) 22
  • 23. IGEM 2005-2008 How does the research being done by the students in Synthetic Biology. Meanwhile, the iGEM lab relate to other projects being pursued TUDelft 2008 stated that ethical under the banner of Synthetic Biology? What does it decisions have to be made mean to be a human practices member of an iGEM throughout the entire project team? Doing Synthetic Biology (experimenting, development. designing projects, situating findings within it, making Finally, Calgary 2008 prepared decisions about what projects are important, etc.) is a two online surveys, one written for high-school human practice. (UCBerkeley 2008). In its Code, students and the other for adults, to better understand Valencia 2008 exposed three general commitments the level of knowledge of Synthetic Biology, what was regarding bioethics: research on Synthetic Biology must forecast about its future, implications and advances not be directed by economic interests, animal dignity and which framework of governance Synthetic Biology must be assured in every synthetic biology-related should have. Valencia 2008 was the first to propose research program and common what they called the Concentric Units of Ethical Issues sense should be followed. whereas UCBerkeley 2008 enumerated the proposals Moreover, there have been from SynBERC and used a blog, a notebook and the several discussions among ArsSynthetica web to follow the development of their terms, as shown in: “ethics of ethical study. consequences” vs. “ethics of And among all these questions, the one that might be principles” (KULeuven 2008), “standardized the ultimate question: Is the world BioBricks” or “standardized prepared for Synthetic Biology? science” (TUDelft 2008) and (Calgary 2008). “bottom-up approach” vs. “top- down approach” (KULeuven 2008). Furthermore, KULeuven 2008 also cited the “Three laws of Robotics” (Isaac Asimov, 1942) and postulated justice, autonomy and culture as the three central ideas that are present in all debates concerning ethics and 23
  • 24. HUMAN PRACTICES In 2008, a “Best Human Practices Advance” was recognized for the first time in the iGEM competition as a special prize. The Heidelberg team won this award for a report on Synthetic Biology and scientific communication, in which they discussed the role of the media in scientific dissemination as well as people’s opinion and knowledge about Synthetic Biology. They CONCLUSIONS also included surveys and an interview of a Nobel Prize winner. Human Practices are becoming more and more The four topics listed in our review (SB & iGEM, important in the iGEM competition. In the first Biosafety & Risks, Patents and Bioethics) have had international edition, in 2005, only the MIT team wrote a different relative importance in each iGEM edition. very brief reference to Biosafety issues in its project. SB & iGEM was mentioned for the first time in three However, since then, there has been an exponential reports in 2006. The number of teams which included increase in the number of teams dealing with this issue, this topic in their work was the same in 2007 but including a Human Practices report. increased in 2008 from three to five reports. 24
  • 25. IGEM 2005-2008 Despite being the only topic cited in 2005, Biosafety & Risks was not included in any of the 2006 reports and just in one of the 2007 edition. However, it has been the most widely discussed issue in 2008 (eleven reports) and also in the whole iGEM competition (a total of thirteen). In 2007, two teams introduced a new issue: Patents. The number of reports on intellectual property doubled in the following iGEM edition. The iGEM community had to wait until 2008 to read some reports on another new topic: Bioethics, which became the second most-discussed issue of that year (seven reports). 25
  • 26. HUMAN PRACTICES The variety of topics included in Human Practices reports has increased every year: 26
  • 27. IGEM 2005-2008 Furthermore, iGEM teams have tried to make Synthetic Biology closer to non scientists by including surveys addressed to the general public (Heidelberg, TUDelft and Calgary 2008); developing a glossary in which terms like Synthetic Biology, Systems Biology, Biotechnology, Metabolic Engineering, System, etc. are defined and briefly explained (Valencia 2008); or by designing a part of the Wiki for people without a strong biological background (Heidelberg 2008). Finally, one of the funniest points of Human Practices reports are quotations, often referring to contemporary science fiction heroes’ ethics, which are used as metaphors of today’s SB challenges. “With great power comes great responsibility” Spiderman’s uncle Ben (Va len cia 2008) “Fear leads to anger. Ange r leads to hate. Hate leads to suffering” Master Yoda (KULeuven 2008) [1] : The Art of Asking Essential Questions. By Linda Elder and Richard Paul. 48 pages. The Foundation for Critical Thinking. 2006. 27
  • 29. 29
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  • 34. THE SURVEY With this survey, we wanted to know people’s opinion who do not know about SB (hereon “informed” vs. on several topics related to Synthetic Biology. That’s “uninformed”), and iGEM members vs. non iGEM why we prepared a short questionnaire which was members. Exceptionally, other groups like those addressed to both iGEM members as well as other informed vs. uninformed about the iGEM competition, people. We tried to write the questions in a clear and engineers vs. life scientists will be differentiated in language, avoiding the use of technical words. some questions. Our survey was available from July 29th to October These are the main results of our survey: 12th in our Wiki. We also sent personalized mails to all Question 1. Do you know what Synthetic Biology 2009 iGEM teams inviting them to fill it in, we posted is? the survey in some important websites such as www.synbiosafe.eu or www.syntheticbiology.org, and A also in well-known social networks like Facebook. We got 1288 answers, which made our survey the biggest one ever made (to the best of our knowledge, the ¿¿Royal Academy of Engineering?? survey, with 1005 participants, was the biggest one ever made before). 643 answers came from members of 101 i G E M 2 0 0 9 t e a m s . We a c k n o w l e d g e d t h e i r collaboration by designing gold (100% of members Question 1 have responded), silver (75%) and bronze medals (50%) for their Wikis (see page 43). The other 645 answers A total of 864 people out of the whole 1288 came from people belonging to many different social participants (67%), asserted they knew what SB is and groups (for more details you can see page 69 of our gave their own definition (these definitions are analyzed Appendix). in page 48). Obviously, almost all iGEM members (98%) Besides considering all the participants’ results in our were able to define SB, whilst the percentage of non analysis, different groups of people were also iGEM members who knew what SB is was substantially distinguished: people who know about SB vs. people lower 36% (see B). 34
  • 35. It has to be noted that considering the people who are not members of iGEM, the percentage of them who B can give a definition of SB was higher (74% vs. 23%) when they also knew about this competition. That shows the important role iGEM plays in the diffusion of this emerging field (see C). Finally, the number of life scientists who knew about SB was higher (81%) than engineers (60%). Regarding people from other fields, less than half (45%) were able to define SB (see D). Question 1 Question 1 D C Question 1 35
  • 36. THE SURVEY A B Question 2 Question 2 Question 2. Now, without looking at Wikipedia… classical Genetic Engineering when they are not clearly select the 5 words you feel are most closely defined. SB can be used for creating transgenics, but so related to Synthetic Biology too could the other disciplines mentioned above. On the other hand, Modeling, Standards or BioBrick specifically DNA, System, BioBrick, Modelling, Standards and refer to SB. Creation are by far the words that people consider more related to SB, followed by Abstraction, PCR and It is important to highlight that very few people, even SB Transgenics (See A). uninformed, propose words like Destruction, Anthrax or Infection. This means that currently people don’t However, there are some differences between SB immediately associate fear or mistrust with the term informed and uninformed people: the latter don’t Synthetic Biology. Furthermore, another difference recognize BioBrick and Standards as SB-related terms, between SB informed and uninformed is the following: if and point out another word: Transgenics. (See B). answers from life scientists and engineers are This fact can be due to their incapacity to distinguish SB compared, there are no significant differences when they from other similar disciplines such as Biotechnology or know what SB is, as it is a deeply interdisciplinary science; however, when SB is unknown, engineers and 36
  • 37. C C Question 2 Question 2 life scientists choose the words more closely related with their own fields. Words such as PCR, System, Modelling and Standards are good examples (see C). Question 3. Knowing that parts of genetic A information can be isolated, do you think these pieces should be patentable or open source? Regarding intellectual property, people agree (74%) in considering that parts of genetic information should be open source. Only 13% of participants think that they should be patentable (see A). Comparing iGEM members and not iGEM members, there is a difference of opinions. A higher percentage of iGEM participants (80% vs. 68%) asserted that parts Question 3 should be open source. This result agrees with the iGEM 37
  • 38. THE SURVEY B ideals on this topic, for instance, the creation of the Registry of Parts, in which anyone can find lots of free standardized parts (see B). The idea of open source is better supported by SB informed (79%) than by SB uninformed (63%). However, it has to be noted that a significant percentage (22%) of the latter ones did not have a clear opinion (see C). No significant differences were found between life scientists and engineers. However, the percentage of people from other fields who believed that genetic parts Question 3 should be open source was lower (64% vs. 80% and 75%) (see D). C D Question 3 Question 3 38
  • 39. Question 4. Let’s assume that humans can create B artificial life. Do we have the right to do it? The creation of artificial life is a more controversial issue. Although most people (63%) assert that human beings have the right to create life in the laboratory, 26% do not approve. Interestingly, a significant 11% of participants were unable to give an answer because of the transcendence and the moral and religious implications of this topic (see A). There are no significant differences between iGEM Question 4 members and non iGEM members (see B). But there is a difference on comparing SB informed and uninformed. The percentage of the latter that agree with the creation of artificial life is not as high (57%) as the former (66%) (see C). A C Question 4 Question 4 39
  • 40. THE SURVEY D A Question 4 Question 5 Furthermore, the percentage of life scientists who Question 6. Do you think there are significant approve of the creation of artificial life (67%) is slightly ethical differences between Classic Genetic higher than the one of engineers (62%) and other fields Engineering and Synthetic Biology? (58%) (see D) On the differences between classic GE and SB, we can Question 5. Do you think is possible a situation conclude that there is a maximum parity between both such as many science-fiction movies as "I, Robot", views. However, 179 people out of 1288 did not "Terminator", etc, in which humans go a step too understand the meaning of the question (see A). far in their need for improving themselves? The vast majority of people (97%) who agree with the creation of artificial life don’t believe that this hypothetical power could lead us to the irrational situation that many science-fiction movies show. 40
  • 41. A B Question 6 Question 6 An interesting finding is that iGEM members and non members have opposite opinions: more than half (52%) of the iGEM members consider that there are no significant ethical differences between SB and classic GE, whilst only the 31% of non iGEM members agree with that (see B). C Another finding is that, despite the number of “What?” responses rate is 22 points higher for those who claim not to know what synthetic biology is, the “Yes” percentage has practically remained the same in both groups (see C). Question 6 41
  • 42. THE SURVEY Question 7. Do you think eating a transgenic Similarly, there is a difference of 17 percent between SB vegetable is harmful for your health? informed vs. uninformed who assert that eating a transgenic vegetable is harmful, which means that Regarding eating transgenic vegetables, more than 60% people knowing about synthetic biology distrust GM of interviewed people believe that they are not harmful food less (see C). for their health, whilst 362 out of 1288 relate their response to a particular case of modified food (see A). The percentage of participants that consider transgenic food dangerous changes among fields: Only 5% of life A surprising result is the high percentage of iGEM scientists do not trust these products, whilst the members and SB informed who chose the third option percentage of engineers and people from other fields (“It depends. I would agree with the Golden Rice, not with this opinion is more than twice and four times with Roundup Ready strains”), as there is no reason for higher, respectively (see D). these vegetables to be more dangerous than other transgenic products. However, the percentage of iGEM Question 8. Do you think eating a drug produced in members that consider transgenic food dangerous is a genetic modified organism (GMO) is dangerous slightly lower (5%) than for non iGEM participants (17%) for your health? (see B). A B Question 7 Question 7 42
  • 43. C Similarly, the majority argues that there is no problem in eating a drug produced in a genetically modified organism. Interestingly, there is a slightly higher percentage (4%) of people against drugs produced in GM than against transgenic vegetables (see A). The results reveal an increased confidence in GMO products (difference of 10%) by those who are iGEM participants compared with those who are not (see B). The same conclusion can be reached on comparing SB informed and uninformed people (see C). Question 7 Once again, there is no agreement between people from different fields. Drugs produced in GMOs are rejected less by life scientists (8%) than by engineers (17%). D A Question 7 Question 8 43
  • 44. THE SURVEY Participants from other fields distrusting this type of Disaggregating the responses by groups in each drugs was higher (28%): ranking, we must point out a clear trend: people with a greater awareness of Synthetic Biology believe that it is Question 9. From 1 (nothing) to 5 (completely) how potentially more beneficial and less dangerous than dangerous or beneficial do you think Synthetic Biology is? Question 8 Only 36 out of 1288 think that Synthetic Biology is a little C or not beneficial at all. But, on the other hand, more than 82% of the opinions see this new area as highly or completely beneficial. Analyzing hazard, we can see that almost 35% have chosen the more neutral option. But if we study the more extreme options, 306 responses out of 1288 say that Synthetic Biology is very or completely dangerous whilst 42% of interviewees consider it not at all or a bit hazardous. B D Question 8 Question 8 44
  • 45. uninformed people. A similar conclusion can be obtained when iGEM members and non members are compared. A Beneficial Question 9 Question 9 B Dangerous Question 9 Question 9 45
  • 46. THE SURVEY Finally we want to th ank all the iGEM te Question 10. Do you think we should continue that have helped us ams research on Synthetic Biology? to fill in this survey. designed some m We edals according to The last question has revealed a virtually total approval collaboration, they their can post them on to continue research in Synthetic Biology. Only 19 out of Wiki if they want. their 1288 disagree with the development of this new discipline. B Gold (100% of the team members have filled our survey): Imperial College London, Paris, Minnesota, Chiba, Harcard, SupBiotech-Paris, NTU Singapore, IPN.UNAM Mexico, Question 10 Sheffield, Heidelberg, DTU Denmark, KU Leuven, Virginia Commonweath, TorontoMaRSDiscovery, UAB Barcelona, Southhampton, Slovenia, SDU Denmark, British Columbia, Wisconsin Madison, Edinburgh, Groningen, Freiburg Bioware, Freiburg Software, UCL London, TU Delft, Calgary, LCG-UNAM Mexico, UQ Australia, Art Science Bangalore, IT Bombay India, Brown, Berkeley Software, BCCS Bristol. Silver (75% of the team members have filled our survey): PKU Beijing, Lethbridge, SJTU Biox Shangai, Upsala Sweden, Victoria Australia. Bronze (50% of the team members have filled our survey): Cambridge, Missouri Miners, Wash U, Victoria BC, NYMU Taipei, EPF Lausanne, Yeshiva NTC, Mo Western Davidson, Virginia U Chicago, Bay Arka RSI, Michigan, Queens, Johns Hopkins Bagm Bologna, USTC, Biotec Dresden, USTC Software, IIT Madras, Washington, ULB Brussels, UC Davis. *643 Members from all iGEM Teams have answered to our survey (58% of the total) 46
  • 47. CONCLUSIONS Other works with a similar goal have been published this year[1], [2]. In their surveys, fewer people participated (16 personally and 1005 interviewed by telephone[1], and In our opinion, Synthetic Biology is a novel discipline that 1001[2]) and they were only addressed to UK[1] and is beginning to be well-known among society. The USA[2]. Synthetic Biology: public dialogue on Synthetic general public does not seem to be afraid of SB, even Biology[1] is the first UK’s public dialogue of Synthetic though it is a revolutionary area. However, a lot of people Biology that explores people’s views and attitudes do not have a clear idea of what it is, so more efforts towards this discipline. It was carried out by The Royal should be addressed to disseminating this new field. Academy of Engineering (www.raeng.org.uk). Its objectives were to determine public awareness of SB, Similar answers were found among different groups explore uninformed and informed public attitudes to SB, when we asked them about creating life in the laboratory identify particular hopes, expectations and concerns and problems regarding intellectual property. We think relating to the development of the technology, and that these profound issues are strong convictions identify issues that merit further research and/or formed early in life and are hard to change. This dialogue activity. contrasts with questions related to transgenics. One can clearly see how different answers may be in terms of Finally, Nanotechnology, Synthetic Biology, & Public participants’ biotechnological knowledge and the field Opinion[2] is a report of findings based on a survey. It they are working on. When we asked about ethical was conducted on behalf of The Woodrow Wilson differences between Synthetic Biology and classic International Center for Scholars. This is the fourth year Genetic Engineering, we also found diverging answers of the study, but since the second year it included depending on the social group. According to this Synthetic Biology. They basically asked about public information, we may classify ethical questions in two awareness of SB (with similar results to [1], not a lot of blocks; when positions are extreme and a debate is people know about it), the impression of its risks and usually futile we have “insurmountable issues”, on the benefits, and concerns about biofuels. Like us, they other hand, when opinions change depending on concluded that there should be more information for the knowledge of the topic we consider these as “relaxed general public about new technologies. issues”. 47
  • 48. THE SURVEY DEFINITIONS three of the divisions established. We were not able to find any definition that referred to the four criteria. After considering and comparing all definitions received (864) they were classified into four different groups. Characteristic SB concepts. and the design of new systems. Rationalizing biological Engineering processes. approach to biology. Thus, over 65% of the responses have been included in one or more of these segments. Obviously, groups are not mutually exclusive and one definition may fall into more than one group. However, 66% of the definitions were classified in a single group, 22% into two main groups, and only 4% were considered to correspond to You can check all the 863 definitions at http://2009.igem.org/Team:Valencia/All_Definitions 48
  • 49. In a more detailed analysis, more than half of the answers dealt with the design and creation of new systems (58%); 48% on the relationship between Synthetic Biology and Engineering; 19% were descriptive definitions listing some of the basic features of this new discipline such as “standardization” and “abstraction”; and 8% included the importance of Synthetic Biology in “understanding” biological systems. Words used to define SB among each of the four groups are listed below. Synthetic Biology and the design of new systems. Within this section, participants have tions defined Synthetic The best defini Biology as creation (38%), designing (33%), “A new interdisciplinary field that involves the design, construction and engineering (32%), building standardization of new biological parts, devices, and systems, and the re- (14%), modifying (13%), design of existing, natural biological systems for useful purposes.” making (8%) and assembling Female, undergraduate student, under 20 years old (2%) new biological systems (56%), parts (28%), “Application of engineering principles (modularity, abstraction) to organisms (18%), devices rationalize the art of genetic modification, increasing the complexity of (17%), functions (16%), life systems that can be designed and constructed reliably.” forms (12%), components Male, doctoral degree, 31-40 years old (7%) and machines (4%). “Synthetic biology is a new discipline of life sciences focused on bringing Engineering approach to engineering into biology. It uses engineering concepts like modeling and Biology. standardization to create biological devices with new capabilities that do not exist in nature.” This group includes definitions referring to Male, graduate student – Ph, 21-30 years old Synthetic Biology as a new interdisciplinary field where 49
  • 50. THE SURVEY Rationalizing biological processes. The last group corresponds to those definitions that consider Synthetic Biology as a field of knowledge that aims to further understand biological systems (70%), the basis of life (18%) and complex biochemical pathways (12%). inal definitions The most orig “Engineering + Cell Biology - World Domination.” Male, graduate student – Ph, 21-30 years old “Decouple life, Construct life.” engineering principles are applied to Biology (69%), Male, undergraduate student, under 20 years old Biological Systems (39%), Science (7%), Genetic “Synthetic Biology is Systems biology in reverse Manipulation (6%) and Life Sciences (5%). - obtaining in vivo results by in silico prediction.” Characteristic concepts of Synthetic Biology. Male, undergraduate student, 21-30 years old This group includes definitions which state that Synthetic “Abstracting biology concepts with an Biology involves standardization (72%), abstraction engineering framework to introduce standards (16%), modularity (14%), modeling (12%), into the field. Like lego.” characterization (5%), interchangeability (3%), Male, undergraduate student, under 20 years old automation, insulation, transferability, hierarchy, acceleration and simulation of biological systems (2%). “Thinking like an engineer and doing like a molecular biologist.” Female, doctoral degree, 31-40 years old 50
  • 51. using organisms systems construction novel existing biology design science create genetic life devices parts synthetic new functions natural Base: All respondants (1288) The most repeted words in all of our 863 definitions. Size according to its repetition. “Biology” refers to both “biology and “biological” terms. This word cloud was created by http://www.wordle.net/ [1] : Synthetic Biology: public dialogue on synthetic biology. The Royal academy of Engineering. 60 pages. 2009. [2]: Awareness of and Attitudes Towards Nanotechnology and Synthetic Biology, Peter D Hart Research Associates. Inc. 17 Pages. Woodrow Wilson International Center for Scholars. 2009. 51
  • 52. THE EXPERTS Markus Schmidt Antoine Danchin Markus Smicht is an Austrian biosafety scientist. His research interests include plant genetic resources,  risk assessment, public perception, communication, and technology assessment (TA) of novel bio- and nanotechnologies, including Synthetic Biology. His interest in SB is beyond doubt and he has interviewed many experts in the field (http:// www.synbiosafe.eu/index.php?page=expert-interviews) With more than three hundred publications in forty years, Antoine Danchin is nowadays, one of the most popular scientists developing theoretical reflections and experiments in the domain of Synthetic Biology. Trained as a mathematician and a physicist, his work with Adenylate cyclase is well known, but he has also focused on Bioinformatics and Philosophy of Science. Both of them have kindly answered an interview about Synthetic Biology. First, we have asked them to fill in our survey. If you answered it too, you may be interested in comparing your answers with the ones of our experts. Finally, we have asked several additional questions on Ethics, Biosafety and the Regulatory frameworks of Synthetic Biology. 52
  • 53. ANSWERS TO OUR SURVEY Question: Do you know what Question: Do you know what Synthetic Biology is? Please, Synthetic Biology is? Please, define it! define it! Answer: Yes, Synthetic biology is the Answer: Yes,  is the process to design and construction of new reconstruct life from the chemical biological systems not found in world. Markus nature. It aims at creating novel Antoine organisms for practical purposes but also at gaining insights into living systems by re- constructing them. SB is an interdisciplinary field, involving microbiology, genetic engineering, information technology, nanotechnology, and biochemistry. SB as a scientific and engineering field includes the following subfields: (A) Engineering DNA-based biological circuits, including but not limited to standardized biological parts; (B) Defining a minimal genome/minimal life (top-down approach); (C) Constructing so-called protocells, i.e. living cells, As they ar e experts, M from scratch (bottom-up approach); like to foll arkus and (D) Creating orthogonal biological systems based on a ow the rule Antoine do answers fu s! They ha n’t biochemistry not found in nature (e.g. non-DNA, non- rther than ve extended But since requested their RNA nucleic acids); and we think th in the sur (E) Gene and Genome DNA synthesis valuable, w eir ideas a vey. e have inclu re particula read. ded them f rly or all of yo u to 53
  • 54. THE EXPERTS Q: Now, without looking at Q: Now, without looking at Wikipedia, select the 5 words you Wikipedia, select the 5 words you feel are most closely related to feel are most closely related to Synthetic Biology. (Answers in bold) Synthetic Biology. (Answers in bold) A: DNA, Plastic, Destruction, A: DNA, Plastic, Destruction, Abstraction, Anthrax, System, Abstraction, Anthrax, System, Markus PCR, Infection, BioBrick, PCR, Infection, BioBrick, Antoine M o d e l l i n g , Tr a n s g e n i c s , Modelling, Transgenics, Creation, Creation, Standards. Standards.   Q: Knowing that parts of the genetic information Q: Knowing that parts of the genetic information can be isolated, do you think these can be isolated, do you think these pieces should pieces should be ... ? be ... ? A: Patentable // Open Source // Sorry, I don't A: Patentable // Open Source // Sorry, I don't know. know. One can only patent the result of inventive activity. Therefore isolated genetic information cannot be Q: Let´s assume that humans can create artificial patented as such, but only coupled to some kind of life. Do we have the right to do so? inventive activity. A: Yes // No // Sorry, it's too hard for me. Q: Let´s assume that humans can create artificial Q: Do you think the situation shown in many life. Do we have the right to do so? science fiction movies A: Yes // No // Sorry, it's too hard for me. “SB tries to much more is possible, like "I, Robot", "Terminator", Q: Do you think the situation shown in many rational than Genetic etc, in which humans science fiction movies is possible, like "I, Robot", go a step too far in "Terminator", etc, in which humans go a step too Engeneering.” far in their need for improving themselves? their need for (Markus) improving themselves? 54