SYNTHETIC BIOLOGY: BEYOND GENETIC ENGINEERING

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SYNTHETIC BIOLOGY: B
EYOND GENETIC
ENGINEERING

TECHNYOU

JULY 2012


free call: 1800 631 276

www.technyou.edu.au




Synthetic biology: beyond genetic engineering

1

Synthetic biology is where science blends biology, genetics, nanoscience and
engineering. Instead of installing a handful of genes with specific functions as you would
do to make a genetically modified organism (GMO), synthetic
biology is more about
systems biology
-

putting novel genetic systems and metabolic pathways into organisms.
In this field, scientists are trying to rewrite the genetic code, though one must be careful
of suggesting it is about creating life. For the fores
eeable future it will remain, at most,
an extreme form of genetic engineering with the aim to improve such things as medical
technologies, human health, food production and environmental monitoring.

As for a definition, it is such a new and fast evolving f
ield that there doesn't appear to be
a standard definition for it. But here is one from the UK Royal Society:

"Synthetic biology is an emerging area of research that can broadly be described as the
design and construction of novel artificial biological pat
hways, organisms or devices, or
the redesign of existing natural biological systems."

So, the big questions are what can we do with synthetic biology that would otherwise be
impossible; what should we do with these technologies; and what might the implicat
ions
be for society?

What can we do now?

The answer is not much relative to the hopes and dreams of the scientists working in this
field, but this is the nature of science. There is a lot of basic knowledge to obtain before
any practical applications can
become a reality.

At the moment, the key question for researchers in this field is not how a biological
system functions, but rather working out what is the minimum set of genes that a living
thing requires to exist and replicate? Then the engineer can con
sider how to integrate
into that life the genetic functions they require.

The applications. What have we managed so far?

To date, nearly all research has focused on single
-
celled organisms (prokaryotes) such as
bacteria. Eukaryotes, or organisms whose nucl
eus and other important cellular parts are
bound in membranes and include everything from algae to humans, are dauntingly
complex and synthetic biology applications with these beasts requires a step up in
understanding that we have yet to reach, though res
earch is being done. The exception
here is yeasts which are single
-
celled Eukaryotes.

Meet Synthia

Craig Venter of the J Craig Venter Institute made a synthetic cell by stitching together
the genome of a goat pathogen from smaller stretches of DNA synthesi
sed in the lab.
1

This was then inserted into the empty cytoplasm of a related bacterium
-

one that has
had all of its DNA material removed. The transplanted genome then fired up in the host
cell and divided continually making copies of the original goat pa
thogen.

Remarkable as this was it wasn't artificial life. As Venter himself noted, the genome was
largely copied from an existing one without really knowing what all the genetic parts did.
There is a long way to go before we can pull known parts off the sh
elf to make a novel,
self
-
replicating organism with select functions.

Synthetic biology: beyond genetic engineering

2

Venter's research teams want to use synthetic DNA to build a "minimal genome," which
will include only the genetic material needed to sustain the life of a bacterium. It will
then be
just a matter of plugging in the genetic parts for the various desired functions
such as making fuels, though you can be assured it will be more complicated than it
sounds here.
2

Synthetic yeast will evolve on command

Biologists have built two artificial c
hromosome arms and inserted them into living yeast.
They intend to replace the entire yeast genome over the next few years and then evolve
new strains to order. As well as designing and building the new genome from scratch, the
team has come up with a way
to systematically scramble it to produce new strains. This
work is being led by a team at Johns Hopkins University School of Medicine in Baltimore,
USA.
3,4

Medicine

Synthetic biology strategies have been developed to target infectious diseases, cancer,
vac
cine development, cell therapy, and regenerative medicine, though most of the
research is still a long way from the clinic.

Artemisinin. An Anti
-
malaria drug

Artemisinin is extracted from the wormwood tree (Artemisia annua) native to temperate
Asia and is
used as a herbal remedy to treat malaria.

Attempts to synthesize it chemically have proved too expensive to make it viable and
supply shortages of the drug are common. A team from University California Berkeley
engineered metabolic pathways with about 12 g
enes from the wormwood and elsewhere
and inserted them into yeast. The metabolic pathway in the yeast churns out the
chemical artemisinic acid, which can then be easily synthesized into artemisinin.
Synthetic artemisinin is expected to be available commerc
ially in 2012.
5

Anti
-
bacterials

Bacteriophages


viruses that only infect specific bacteria


have been

engineered to
attack or weaken
bacterial strains resistant to antibiotics by disrupting their antibiotic
defence mechanisms. In an initial study, bacte
riophages were engineered to degrade
bacterial biofilms and kill off bacterial cells in the biofilm. Biofilms, which play a critical
role in the pathogenesis of many persistent infections, are bacterial communities
encapsulated in a slimy matrix that shiel
d bacteria from attack by host immune systems
and antibiotics. This research reported that the double action of degrading the biofilm
and killing the bacteria eventually removed 99.997% of bacterial cells.
6

Biofuels

Research groups worldwide are attempting

to use synthetic biology tools to develop
bacteria that can make biofuels.

The Australian Institute for Bioengineering and Nanotechnology (AIBN) is engineering
yeast and E. coli cells for the production of industrial chemicals to replace petrochemical
sou
rces. Specifically they are using these organisms to make the catalysts used to help
convert sucrose to compounds that they will use for the production of synthetic rubbers
Synthetic biology: beyond genetic engineering

3

and aviation fuel. Part of this research involves development of a genetic 'cassett
e' that
can be plugged into these micro
-
organisms to manufacture these compounds.
7

Elsewhere, US researchers from the University of Washington and the company, Bio
Architecture Lab Inc. have engineered E.coli to digest seaweed and turn it into biofuels.
Se
aweed contains the sugars glucan, mannitol and alginate, with the latter two being
difficult to digest and get biofuels from. Fortunately, researchers found marine bacteria
with the genes that could perform many of these tasks. The tricky bit was getting t
he
genes responsible into the industrial workhorse, E.coli, so the system could work at an
industrial scale. This required constructing multi
-
gene components comprising over 20
genes, and to complete their model E.coli they added a fermentation pathway and

deleted some of its genes they thought might interfere with the whole process. In the
end it worked with the bacteria churning out 0.64g/litre/hour, representing over 80% of
the maximum possible yield. Whether this will ultimately be viable is another mat
ter as
there are environmental and social issues to consider such as the consequences of
growing and harvesting the seaweed needed.
8

What lies ahead?

At the moment our research is simply tinkering within the genetic capabilities of existing
organisms. One
goal is to construct from scratch a completely novel organism with genes
and biological systems not found in nature. For example, why should we be restricted to
the basic 20 amino acids that evolution has provided to build our proteins? Some
scientists are

suggesting we can mix and match. If a synthetic polymer or piece of
engineered DNA origami can perform a task as well or better than the regular fat and
protein systems, why not build a system from the bottom up that incorporates these
synthetic component
s
-

a cyBorg Bacteria. Others are trying to figure out how to
construct artificial chromosomes that carry a suite of novel genes. Some of these might
augment human traits such as strength, immune systems or the more aesthetic traits.
9

How far away all this

is from reality is hard to predict.

Biobricks

Biobricks is based on the concept of Lego® where any part can attach to any other via
some universal connector. Biobricks

are chunks of DNA that, for example, might have
one or more genes, or genetic switches that turn genes on or off to varying degrees. On
each end are specific bits of DNA code that act as the universal connectors. You can join
these Biobricks together or s
lot them into the existing genome of a living organism.
Biobricks is an attempt to have a library of standardised biological parts with specific
functions that people can order. Many of these parts may not exist in nature.

The BioBricks Foundation has give
n itself the job of ensuring that the engineering of
biology is conducted in an open and ethical manner to benefit all people. Website:
http://biobricks.org/


The Biobrick parts can be found at the Registry of Bioparts

at Massachusetts Institute of
Technology (MIT). The Registry has more than 5000 parts available, but it can't
guarantee their quality or even if the parts will work as they are supposed to. One of
reasons for this is because many of parts are made by unde
rgraduate students
participating in the competition, International Genetically Engineered Machine (iGEM).

Even with parts that do work they will often behave differently when plugged into
different living systems, different cell types or exposed to differe
nt environmental
Synthetic biology: beyond genetic engineering

4

conditions. One way scientists are trying to circumvent this is to physically isolate the
synthetic system from the cellular machinery by creating cellular membrane
-
bound
compartments to house the synthetic system within the host cell
10

Ma
naging risks

When the day comes that we can make true synthetic life in the lab, or ultimately an
industrial factory, how do we make sure it stays there and only the desired products of
the synthetic genes reach us? No technology, in fact nothing full stop
, is risk free.
Synthetic biology, however, does result in living things that have the potential to breed
(though bacteria divide rather than breed). Research groups have proposed many ways
to manage this risk including engineering synthetic bacteria to on
ly divide a certain
number of times before death, or to engineer them to only survive in the presence of a
certain chemical provided in the laboratory.

Nothing is foolproof. Two key questions are what level of oversight is appropriate; and
what level of ri
sk are we prepared to accept? The answer to this will be different for each
person, and no doubt for the application the synthetic life is used for. Will our risk
perception differ for synthetic organisms that produce a drug to treat cancer compared to
one

that can produce a biofuel? We all interpret risk differently.

Regulation

Australia doesn't have legislation or regulatory guidelines specific to synthetic DNA,
though any research involving genetically modified organisms is regulated by the Office
of the

Gene Technology Regulator that operates according to the
Gene Technology Act
2000.

OGTR's description of the act:
The Gene Technology Act 2000,
which came into force
on 21 June 2001, introduces a national scheme for the regulation of genetically modified
organisms in Australia to protect the health and safety of Australians and the Australian
environment by identifying risks posed by or as a result of gene technology, and by
managing those risks through regulating certain dealings with genetically modified

organisms.

The Australian government has a regulatory scheme called Security Sensitive Biological
Agents (SSBA) controlled by Department of Health and Ageing (DHA). DHA implemented
the scheme to improve the security of biological agents of security concer
n in Australia.
They don't have any regulatory powers that include synthetic biology, but they do keep
tabs on biowarfare agents, foot and mouth, viruses and other nasty agents. It all falls
under the
National Health Security Act 2007.

The Australian gover
nment is also the informal chair of the Australia group, a group of 40
countries and the European Commission that is a cooperative and voluntary body
dedicated to the adoption, implementation and enforcement of cutting
-
edge measures to
counter the spread o
f technologies and materials that could assist states of concern and
terrorist groups in obtaining or developing chemical and biological weapons.
11

In a recent
meeting they agreed to form a synthetic biology advisory body as a means of ensuring
the Group i
s kept abreast of, and can respond quickly and appropriately to, technological
developments in this area.

Synthetic biology: beyond genetic engineering

5

Backyard biotech: The rise of the biohacker

There is a large, active and vibrant community of backyard biotechnologists throughout
the world, some more organised than others. Known as 'Biohackers', this group of citizen
scientists tinker with synthetic biology tools and biological parts such as gene
s to create
novel biological systems, though most are doing nothing more harmful than DNA
extraction.

Examples include everything from making bioluminescent yogurt to arsenic biodetectors.
One self
-
proclaimed biohacker, Meredith Patterson, is conducting ex
periments in her
kitchen on a budget of less than $200. She is attempting to transform yogurt bacteria to
signal the presence of melamine, the toxic stuff found in dairy products in China a couple
of years ago.
12

But the ability to get into the riskier stu
ff could become easier as equipment costs
continue to plummet, our understanding of genetics increases and the plug and play
genetic parts already available get a bit more sophisticated and reliable.

For instance, gel electrophoresis kits (the tool used to

separate out specific sized chunks
of DNA or proteins) can now be bought from toy shops and many high schools have
them. The DNA synthesizing machine is what you will need to make your DNA strands,
which could be genes or bits of RNA that control how your

genes work. You can get a
small or older model DNA synthesizer on e
-
Bay for less than $1000. PCR machines (your
DNA photocopier) can be even cheaper. Or you can simply bypass this step. For a few
cents per nucleotide (The A, G, T, C that make up DNA), the
re are companies that will
synthesize your genes or DNA sequences for you and ship them to you anywhere in the
world, though not to a home address. You can pick up a centrifuge for about $50 that
hooks up to your drill. A lot of chemical supplies are easil
y bought online or local supplier
and in Australia, at least, there are companies that sell small quantities for schools and
people like me.

Live in a shoebox? No problem, there are organisations that rent out lab space with all
the machines that go bing

that specifically target themselves to biohackers.

There is even an iPhone app to check the compatibility of chemicals so you don't burn
down or blow up your garage or worse, your Mum's kitchen.

This sort of science is no longer just the domain of those w
ith access to well
-
funded
university or industry laboratories. Nor do you require a PhD or similar educational
background. The how to bit is easily sourced from an extensive network of support
groups all just a mouse click away.

More information

DIY Bio
http://diybio.org/


Biocurious
-

http://biocurious.org/


Any biohacking activity will come under the auspices of Australia's Office of the Gene
Technology Regulator, and people involve
d should familiarise themselves with and
comply with the regulatory requirements.

Synthetic biology: beyond genetic engineering

6

Ethics and issues

Many of today's emerging sciences and technologies are converging: Nano
-
, gene
-
,
neuro
-
, engineering, information technology and now synthetic biology, if indeed you can
separate the latter from the rest at all. Hence, it is questionable if there should be a
separate set of ethical questions for each. Most sources for this publication sugge
st there
isn't. The science is interconnected, therefore a set of ethics could apply to any emerging
technology, though some ethical questions will carry more importance in specific contexts
than others.

The big picture question that applies to any technol
ogy is how should society use it? This
is highly subjective of course because we each adopt different ethical frameworks that
form a set of personal values and makes what is an acceptable use different between
people.

Getting philosophical

Delving a bit de
eper you get into the questions of who benefits, who is harmed, and
these can refer to physical and non
-
physical benefits and harms. This can include fair and
equal access to the technology, and who should have control over it. For example, if it is
a new
drug, or system for producing clean water, will all people have access to it and be
able to afford if they do.

In applications such as synthetic biology, as with genetically modified foods, there is
often the discussion of humans' relationship with the nat
ural world and whether we are
breaching some limit with our tinkering. These are all subjective and values
-
based
concepts and apply to tinkering with any living thing including humans.

How should humans view the natural world, of which we are a part? Is it

ours to mould
and modify and, if so, to what extent?

Boldt and M
ü
ller argue that if we use synthetic biology to create lower forms of life and
to think of them as "artifacts", then in the future this could lead to a weakening of
society's respect for high
er forms of life as they naturally occur, including humans.
13

Could it?

The final word

One of the discipline's pioneers, Drew Endy of Stanford University, summed up his
thoughts about synthetic biology in the New Yorker: "It's scary as hell. It's the coole
st
platform science has ever produced, but the questions it raises are the hardest to
answer."
14

References

1.

J Craig Venter Institute
-

http://www.jcvi.org/


2.

Meet Synthia. from New Sci

http://www.newscientist.com/article/mg20627622.600
-
special
-
report
-
where
-
next
-
for
-
synthetic
-
life.html?full=true#bx276226B1


Synthetic biology: beyond genetic engineering

7

3.

http://www.newscientist.com/article/dn20909
-
synthetic
-
yeast
-
will
-
evolve
-
on
-
command.html


4.

Dymond, J. Et al. Synthetic chromosome arms function in yeast and generate
phenotypic
diversity by design. Nature 477, 471
-
476, (22 September 2011)

5.

http://berkeley.edu/news/media/releases/2006/04/12_malaria.sht ml

Synthethic Biology Engineering Research Centre:
http://www.synberc.org/


6.

T. K. Lu, J. J. Collins , Dispersing biofilms with engineered enzymatic
bacteriophage. Proc. Natl. Acad. Sci. U.S.A. 104, 11197 (2007).

7.

http://web.aibn.uq.edu.au/cssb/Projects/Sucrose.html

http://web.aibn.uq.edu.au/cssb/Projects/Isoprenoid.ht ml

8.

Wargacki, A, et al. An Engineered Microbial Platform for Direct Biofuel Production
from Brown Macroalgae. Science 20 January 2012: Vo
l. 335 no. 6066 pp. 308
-
313.

9.

Gregory Stock, Redesigning Humans: Choosing Our Genes, Changing Our Future,
New York: First Mariner Books, 2003.

10.

Biobricks and iGEM:
http://partsregistry.org/Main_Page


http://biobricks.org/


11.

The Australia Group:
http://www.australiagroup.net/


12.

Meridith Patterson:
http://en.wikipedia.org/wiki/Meredith_L._Patterson


From New Scientist
-

http://www.newscientist.com/article/mg20126881.400
-
genetic
-
manpulation
-
now
-
becoming
-
a
-
hobby.html
?


13.

Joachim Boldt and Oliver M
ü
ller, "Newtons of the Leaves of Grass," Nature
Biotechnology 26, no. 4 (2008): 387
-
389.

14.

Specter, M. A life of its own. Where will synthetic biology lead us?

The New Yorker
28 September 2009, 56.
(
http://www.newyorker.com/reporting/2009/09/28/090928fa_fact_specter
)

Other information sources

Synbiosafe:
http://www.synbiosafe.eu/


Another project involved modifying the bacteria in yogurt to make vitamin C from:
Anderson, T. Darning Genes: Biology for the homebody. h+ Magazine, Issue 3 Summer
2009, pp 34
-
36

Phil McKenna, Rise of the garage genome hackers, 7 January 2009

http://www.synbioproject.org/


More information

TechNyou also has files of media clippings, research reports, peer reviewed
papers and fact sheets on a range of emerging technology topics

Synthetic biology: beyond genetic engineering

8

Further discussion on synthetic biology and other emerging technologies can be
found at the TechNyou web site and blog:

www.technyou.edu.au

free call: 1800 631 276

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