Synthetic biology
Encyclopedia
Synthetic biology is a new area of biological
research that combines science
and engineering
. It encompasses a variety of different approaches, methodologies, and disciplines with a variety of definitions. What they all have in common, however, is that they see synthetic biology as the design and construction of new biological functions and systems not found in nature.
s’s publication of « Théorie physico-chimique de la vie et générations spontanées » (1910) and « La Biologie Synthétique » (1912). In 1974, the Polish geneticist Waclaw Szybalski
used the term "synthetic biology", writing:
When in 1978 the Nobel Prize in Physiology or Medicine
was awarded to Arber
, Nathans
and Smith
for the discovery of restriction enzyme
s, Waclaw Szybalski wrote in an editorial comment in the journal Gene:
is one good example of such work. Elowitz had a model for how gene expression should work inside living cells. To test his model, he built a piece of DNA in accordance with his model, placed the DNA inside living cells, and watched what happened. Slight differences between observation and expectation highlight new science that may be well worth doing. Work of this sort often makes good use of mathematics to predict and study the dynamics of the biological system before experimentally constructing it. A wide variety of mathematical descriptions have been used with varying accuracy, including graph theory
, Boolean network
s, ordinary differential equation
s, stochastic differential equation
s, and Master equation
s (in order of increasing accuracy). Good examples include the work of Adam Arkin, Jim Collins and Alexander van Oudenaarden. See also the PBS Nova special on artificial life.
s that are made up of chemicals. Around the turn of the 20th century, the science of chemistry
went through a transition from studying natural chemicals to trying to design and build new chemicals. This transition led to the field of synthetic chemistry. In the same tradition, some aspects of synthetic biology can be viewed as an extension and application of synthetic chemistry to biology, and include work ranging from the creation of useful new biochemicals to studying the origins of life.
Eric Kool's group at Stanford
, the Foundation for Applied Molecular Evolution, Carlos Bustamante's group at Berkeley
, Jack Szostak's group at Harvard
, and David McMillen's group at University of Toronto are good examples of this tradition.
Much of the improved economics and versatility of synthetic biology is driven by ongoing improvements in gene synthesis
.
, who redesigned the Type III secretion
system used by Salmonella
typhimurium to secrete spider silk proteins, a strong elastic biomaterial, instead of its own natural infectious proteins. One aspect of Synthetic Biology which distinguishes it from conventional genetic engineering
is a heavy emphasis on developing foundational technologies that make the engineering of biology easier and more reliable. Good examples of engineering in synthetic biology include the pioneering work of Tim Gardner and Jim Collins
on an engineered genetic toggle switch, a riboregulator
, the Registry of Standard Biological Parts, and the International Genetically Engineered Machine competition (iGEM).
Studies in synthetic biology can be subdivided into broad classifications according to the approach they take to the problem at hand: photocell design, biomolecular engineering, genome engineering, and biomolecular-design. The photocell approach includes projects to make self-replicating systems from entirely synthetic components. Biomolecular engineering includes approaches which aim to create a toolkit of functional units that can be introduced to present new orthogonal functions in living cells. Genome engineering includes approaches to construct synthetic chromosomes for whole or minimal organisms. Biomolecular-design approach refers to the general idea of the de novo design and combination of biomolecular components. The task of each of these approaches is similar: To create a more synthetic entry at a higher level of complexity by manipulating a part of the proceeding level.
, a process sometimes used to improve computer software.
Drew Endy
and his group have done some preliminary work on re-writing (e.g., Refactoring Bacteriophage T7).
Oligonucleotides harvested from a photolithographic or inkjet manufactured DNA chip combined with DNA mismatch error-correction allows inexpensive large-scale changes of codons in genetic systems to improve gene expression
or incorporate novel amino-acids (see George Church
's and Anthony Forster's synthetic cell projects. As in the T7 example above, this favors a synthesis-from-scratch approach.
of biological parts and hierarchical abstraction to permit using those parts in increasingly complex synthetic systems. Achieving this is greatly aided by basic technologies of reading and writing of DNA (sequencing and fabrication), which are improving in price/performance exponentially (Kurzweil 2001). Measurements under a variety of conditions are needed for accurate modeling and computer-aided-design (CAD).
is determining the order of the nucleotide
bases in a molecule of DNA
. Synthetic biologists make use of DNA sequencing in their work in several ways. First, large-scale genome sequencing efforts continue to provide a wealth of information on naturally occurring organisms. This information provides a rich substrate from which synthetic biologists can construct parts and devices. Second, synthetic biologists use sequencing to verify that they fabricated their engineered system as intended. Third, fast, cheap and reliable sequencing can also facilitate rapid detection and identification of synthetic systems and organisms.
and assembly of fragments of DNA, in a process commonly referred to as gene synthesis
.
In 2000, researchers at Washington University, mentioned synthesis of the 9.6 kbp Hepatitis C virus genome from chemically synthesized 60 to 80-mers. In 2002 researchers at SUNY Stony Brook succeeded in synthesizing the 7741 base poliovirus
genome from its published sequence, producing the second synthetic genome. This took about two years of painstaking work. In 2003 the 5386 bp genome of the bacteriophage
Phi X 174 was assembled in about two weeks. In 2006, the same team, at the J. Craig Venter Institute
, has constructed and patented a synthetic genome of a novel minimal bacterium, Mycoplasma laboratorium
and is working on getting it functioning in a living cell.
In 2007 it was reported that several companies were offering the synthesis of genetic sequences
up to 2000 bp long, for a price of about $1 per base pair and a turnaround time of less than two weeks.
By September 2009, the price had dropped to less than $0.50 per base pair with some improvement in turn around time. Not only is the price judged lower than the cost of conventional cDNA cloning, the economics make it practical for researchers to design and purchase multiple variants of the same sequence to identify genes or proteins with optimized performance.
In 2010, Venter's group announced they had been able to assemble a complete genome of millions of base pairs, insert it into a cell, and cause that cell to start replicating.
and flow cytometry
are examples of useful measurement technologies.
is a method used frequently by geneticist
s to obtain large quantities of a particular strand of DNA
. It involves shaping a selected piece of DNA and inserting it into the DNA of a bacterium called a plasmid
. Once the alien DNA is inserted the bacteria is allowed to replicate
thus replicating the DNA that it contains. After replication is completed the copies of foreign DNA are separated from the plasmid. In this sense the bacteria becomes a cyborg because a foreign element is introduced and interacts with the bacteria.
The Sleeping Beauty transposon system
is an example of an engineered enzyme for inserting precise DNA sequences into genomes of vertebrate animals. The SB transposon
is a synthetic sequence that was created based on deriving a consensus sequence of extinct Tc1/mariner-type transposons that are found as evolutionary relics in the genomes of most, if not all, vertebrates. This enzyme took about a year to engineer and since its creation has been used for gene transfer, gene discovery, and gene therapy applications
Biosensor
technology is another example of cyborg bacteria. One such sensor created in Oak Ridge National Laboratory
and named “critter on a chip” used a coating of bioluminescent bacteria on a light sensitive computer chip to detect certain petroleum
pollutant
s. When the bacteria sense the pollutant, it lights up and is then processed or amplified. In Australia, biosensors have been created to detect virus
es, bacteria
, hormones, drug
s, and DNA sequences. In the future scientists hope to create chips that can sense toxin
s such as environmental estrogen
s and warfare agents. Even more recently chemists at the University of Nebraska created a humidity gauge by using gold
plated bacteria on a silicon
chip. With a decrease in humidity there was an increase in the circuit flow. One unique feature that separates the chip from the bioluminescent ones is that that after it has been assimilated the bacteria no longer needs to be kept alive for the humidity gauge to work.
Nanotechnology
also has made advances by using cyborgs.. Researchers at the École polytechnique de Montréal
in Canada
have attached a microscopic bead to swimming bacteria. Using a magnetic resonance imaging
machine (MRI) the researchers have been able to use the magnetic properties of the bacteria to direct it to certain locations. The bead has no purpose at the moment but researchers hope store drugs or other viral fighting agents inside so that it may be released at the directed location.
who have called for a global moratorium on developments in the field and for no synthetic organisms to be released from the lab. In 2006 38 civil society organizations authored an open letter opposing voluntary regulation of the field and in 2008 ETC Group released the first critical report on the societal impacts of synthetic biology which they dubbed "Extreme Genetic Engineering".
synthesis began to appear in 2004. A 2007 study compared several policy options for governing the security risks associated with synthetic biology. Other initiatives, such as OpenWetWare, diybio, biopunk, biohack, and possibly others, have attempted to integrate self-regulation in their proliferation of open source
synthetic biology projects. However the distributed and diffuse nature of open-source biotechnology may make it more difficult to track, regulate, or mitigate potential biosafety and biosecurity concerns.
An initiative for self-regulation has been proposed by the International Association Synthetic Biology that suggests some specific measures to be implemented by the synthetic biology industry, especially DNA synthesis companies. Some scientists, however, argue for a more radical and forward looking approaches to improve safety and security issues. They suggest to use not only physical containment as safety measures, but also trophic and semantic containment. Trophic containment includes for example the design of new and more robust forms of auxotrophy
, while semantic containment means the design and construction of completely novel orthogonal life-forms.
Some efforts have been made to engage social issues "upstream" focus on the integral and mutually formative relations among scientific and other human practices. These approaches attempt to invent ongoing and regular forms of collaboration among synthetic biologists, ethicists, political analysts, funders, human scientists and civil society activists. These collaborations have consisted either of intensive, short term meetings, aimed at producing guidelines or regulations, or standing committees whose purpose is limited to protocol review or rule enforcement. Such work has proven valuable in identifying the ways in which synthetic biology intensifies already-known challenges in rDNA technologies. However, these forms are not suited to identifying new challenges as they emerge, and critics worry about uncritical complicity.
An example of efforts to develop ongoing collaboration is the "Human Practices" component of the Synthetic Biology Engineering Research Center in the US and the SYNBIOSAFE project in Europe, coordinated by IDC, that investigated the biosafety, biosecurity and ethical aspects of synthetic biology. A report from the Woodrow Wilson Center and the Hastings Center
, a prestigious bioethics
research institute, found that ethical concerns in synthetic biology have received scant attention.
In January 2009, the Alfred P. Sloan Foundation
funded the Woodrow Wilson Center, the Hastings Center
, and the J. Craig Venter Institute
to examine the public perception, ethics, and policy implications of synthetic biology. Public perception and communication of synthetic biology is the main focus of COSY: Communicating Synthetic Biology, that showed that in the general public synthetic biology is not seen as too different from 'traditional' genetic engineering. To better communicate synthetic biology and its societal ramifications to a broader public, COSY and SYNBIOSAFE published a 38 min. documentary film in October 2009 http://www.synbiosafe.eu/DVD.
After a series of meetings in the fall of 2010, the Presidential Commission for the study of Bioethical Issues released a report, on December 16, to the President calling for enhanced Federal oversight in the emerging field of synthetic biology. The panel that facilitated the production of the report, composed of 13 scientists, ethicists, and public policy experts, said that the very newness of the science, which involves the design and construction of laboratory-made biological parts, gives regulators, ethicists and others time to identify problems early on and craft solutions that can harness the technology for the public good.
Dr. Gutmann said the Commission’s approach recognizes the great potential of synthetic biology, including life saving medicines, and the generally distant risks posed by the field’s current capacity. “Prudent vigilance suggests that federal oversight is needed and can be exercised in a way that is consistent with scientific progress,” she said.
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...
research that combines science
Science
Science is a systematic enterprise that builds and organizes knowledge in the form of testable explanations and predictions about the universe...
and engineering
Engineering
Engineering is the discipline, art, skill and profession of acquiring and applying scientific, mathematical, economic, social, and practical knowledge, in order to design and build structures, machines, devices, systems, materials and processes that safely realize improvements to the lives of...
. It encompasses a variety of different approaches, methodologies, and disciplines with a variety of definitions. What they all have in common, however, is that they see synthetic biology as the design and construction of new biological functions and systems not found in nature.
History
The term "synthetic biology" has a history spanning the twentieth century. The first use was in Stéphane LeducStéphane Leduc
Stéphane Leduc was a French biologist who sought to contribute to understanding of the chemical and physical mechanisms of life. He was a scientist in the fledgling field of synthetic biology, particularly in relation to diffusion and osmosis...
s’s publication of « Théorie physico-chimique de la vie et générations spontanées » (1910) and « La Biologie Synthétique » (1912). In 1974, the Polish geneticist Waclaw Szybalski
Waclaw Szybalski
Wacław Szybalski is a professor of oncology at the McArdle Laboratory for Cancer Research, University of Wisconsin–Madison Medical School.-Life:...
used the term "synthetic biology", writing:
Let me now comment on the question "what next". Up to now we are working on the descriptive phase of molecular biology. ... But the real challenge will start when we enter the synthetic biology phase of research in our field. We will then devise new control elements and add these new modules to the existing genomes or build up wholly new genomes. This would be a field with the unlimited expansion potential and hardly any limitations to building "new better control circuits" and ..... finally other "synthetic" organisms, like a "new better mouse". ... I am not concerned that we will run out of exciting and novel ideas, ... in the synthetic biology, in general.
When in 1978 the Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
was awarded to Arber
Werner Arber
Werner Arber is a Swiss microbiologist and geneticist. Along with American researchers Hamilton Smith and Daniel Nathans, Werner Arber shared the 1978 Nobel Prize in Physiology or Medicine for the discovery of restriction endonucleases...
, Nathans
Daniel Nathans
Daniel Nathans was an American microbiologist.He was born in Wilmington, Delaware, the last of nine children born to Russian Jewish immigrant parents. During the Great Depression his father lost his small business and was unemployed for a long period of time...
and Smith
Hamilton O. Smith
Hamilton Othanel Smith is an American microbiologist and Nobel laureate.Smith was born on August 23, 1931, and graduated from University Laboratory High School of Urbana, Illinois. He attended the University of Illinois at Urbana-Champaign, but in 1950 transferred to the University of California,...
for the discovery of restriction enzyme
Restriction enzyme
A Restriction Enzyme is an enzyme that cuts double-stranded DNA at specific recognition nucleotide sequences known as restriction sites. Such enzymes, found in bacteria and archaea, are thought to have evolved to provide a defense mechanism against invading viruses...
s, Waclaw Szybalski wrote in an editorial comment in the journal Gene:
The work on restriction nucleases not only permits us easily to construct recombinant DNA molecules and to analyze individual genes, but also has led us into the new era of synthetic biology where not only existing genes are described and analyzed but also new gene arrangements can be constructed and evaluated.
Biology
Biologists are interested in learning more about how natural living systems work. One simple, direct way to test our current understanding of a natural living system is to build an instance (or version) of the system in accordance with our current understanding of the system. Michael Elowitz's early work on the RepressilatorRepressilator
The repressilator is a synthetic genetic regulatory network reported in a paper by Michael Elowitz and Stanislas Leibler. This network was designed from scratch to exhibit a stable oscillation which is reported via the expression of green fluorescent protein, and hence acts like an electrical...
is one good example of such work. Elowitz had a model for how gene expression should work inside living cells. To test his model, he built a piece of DNA in accordance with his model, placed the DNA inside living cells, and watched what happened. Slight differences between observation and expectation highlight new science that may be well worth doing. Work of this sort often makes good use of mathematics to predict and study the dynamics of the biological system before experimentally constructing it. A wide variety of mathematical descriptions have been used with varying accuracy, including graph theory
Graph theory
In mathematics and computer science, graph theory is the study of graphs, mathematical structures used to model pairwise relations between objects from a certain collection. A "graph" in this context refers to a collection of vertices or 'nodes' and a collection of edges that connect pairs of...
, Boolean network
Boolean network
A Boolean network consists of a set of Boolean variables whose state is determined by other variables in the network. They are a particular case of discrete dynamical networks, where time and states are discrete, i.e. they have a bijection onto an integer series...
s, ordinary differential equation
Ordinary differential equation
In mathematics, an ordinary differential equation is a relation that contains functions of only one independent variable, and one or more of their derivatives with respect to that variable....
s, stochastic differential equation
Stochastic differential equation
A stochastic differential equation is a differential equation in which one or more of the terms is a stochastic process, thus resulting in a solution which is itself a stochastic process....
s, and Master equation
Master equation
In physics and chemistry and related fields, master equations are used to describe the time-evolution of a system that can be modelled as being in exactly one of countable number of states at any given time, and where switching between states is treated probabilistically...
s (in order of increasing accuracy). Good examples include the work of Adam Arkin, Jim Collins and Alexander van Oudenaarden. See also the PBS Nova special on artificial life.
Chemistry
Biological systems are physical systemPhysical system
In physics, the word system has a technical meaning, namely, it is the portion of the physical universe chosen for analysis. Everything outside the system is known as the environment, which in analysis is ignored except for its effects on the system. The cut between system and the world is a free...
s that are made up of chemicals. Around the turn of the 20th century, the science of chemistry
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
went through a transition from studying natural chemicals to trying to design and build new chemicals. This transition led to the field of synthetic chemistry. In the same tradition, some aspects of synthetic biology can be viewed as an extension and application of synthetic chemistry to biology, and include work ranging from the creation of useful new biochemicals to studying the origins of life.
Eric Kool's group at Stanford
Stanford University
The Leland Stanford Junior University, commonly referred to as Stanford University or Stanford, is a private research university on an campus located near Palo Alto, California. It is situated in the northwestern Santa Clara Valley on the San Francisco Peninsula, approximately northwest of San...
, the Foundation for Applied Molecular Evolution, Carlos Bustamante's group at Berkeley
University of California, Berkeley
The University of California, Berkeley , is a teaching and research university established in 1868 and located in Berkeley, California, USA...
, Jack Szostak's group at Harvard
Harvard University
Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...
, and David McMillen's group at University of Toronto are good examples of this tradition.
Much of the improved economics and versatility of synthetic biology is driven by ongoing improvements in gene synthesis
Gene synthesis
Artificial gene synthesis is the process of synthesizing a gene in vitro without the need for initial template DNA samples. The main method is currently by oligonucleotide synthesis from digital genetic sequences and subsequent annealing of the resultant fragments...
.
Engineering
Engineers view biology as a technology - the systems biotechnology or systems biological engineering . Synthetic Biology includes the broad redefinition and expansion of biotechnology, with the ultimate goals of being able to design and build engineered biological systems that process information, manipulate chemicals, fabricate materials and structures, produce energy, provide food, and maintain and enhance human health and our environment. A good example of these technologies include the work of Chris VoigtChristopher Voigt
Christopher Voigt is an American synthetic biologist, molecular biophysicist, and engineer. He is currently an Associate Professor in the of the with appointments in the and the graduate student programs. His research interests focus on the reprogramming of bacterial organisms to perform...
, who redesigned the Type III secretion
Secretion
Secretion is the process of elaborating, releasing, and oozing chemicals, or a secreted chemical substance from a cell or gland. In contrast to excretion, the substance may have a certain function, rather than being a waste product...
system used by Salmonella
Salmonella
Salmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction...
typhimurium to secrete spider silk proteins, a strong elastic biomaterial, instead of its own natural infectious proteins. One aspect of Synthetic Biology which distinguishes it from conventional genetic engineering
Genetic engineering
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...
is a heavy emphasis on developing foundational technologies that make the engineering of biology easier and more reliable. Good examples of engineering in synthetic biology include the pioneering work of Tim Gardner and Jim Collins
James Collins (Boston University)
James J. Collins is an American bioengineer, Professor of Biomedical Engineering at Boston University, and a Howard Hughes Medical Institute Investigator...
on an engineered genetic toggle switch, a riboregulator
Riboregulator
In molecular biology, a riboregulator is a ribonucleic acid that responds to a signal nucleic acid molecule by Watson-Crick base pairing. A riboregulator may respond to a signal molecule in any number of manners including, translation of the RNA into a protein, activation of a ribozyme, release...
, the Registry of Standard Biological Parts, and the International Genetically Engineered Machine competition (iGEM).
Studies in synthetic biology can be subdivided into broad classifications according to the approach they take to the problem at hand: photocell design, biomolecular engineering, genome engineering, and biomolecular-design. The photocell approach includes projects to make self-replicating systems from entirely synthetic components. Biomolecular engineering includes approaches which aim to create a toolkit of functional units that can be introduced to present new orthogonal functions in living cells. Genome engineering includes approaches to construct synthetic chromosomes for whole or minimal organisms. Biomolecular-design approach refers to the general idea of the de novo design and combination of biomolecular components. The task of each of these approaches is similar: To create a more synthetic entry at a higher level of complexity by manipulating a part of the proceeding level.
Re-writing
Re-writers are Synthetic Biologists who are interested in testing the idea that since natural biological systems are so complicated, we would be better off re-building the natural systems that we care about, from the ground up, in order to provide engineered surrogates that are easier to understand and interact with. Re-writers draw inspiration from refactoringRefactoring
Code refactoring is "disciplined technique for restructuring an existing body of code, altering its internal structure without changing its external behavior", undertaken in order to improve some of the nonfunctional attributes of the software....
, a process sometimes used to improve computer software.
Drew Endy
Drew Endy
Drew Endy is a synthetic biologist.He was a junior fellow for 3 years and later an assistant professor in the Department of Biological Engineering at MIT. In September 2008, he moved to Palo Alto to become an assistant professor in the Department of Bioengineering at Stanford University...
and his group have done some preliminary work on re-writing (e.g., Refactoring Bacteriophage T7).
Oligonucleotides harvested from a photolithographic or inkjet manufactured DNA chip combined with DNA mismatch error-correction allows inexpensive large-scale changes of codons in genetic systems to improve gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
or incorporate novel amino-acids (see George Church
George Church
George Church is an American molecular geneticist. He is currently Professor of Genetics at Harvard Medical School, Professor of Health Sciences and Technology at Harvard and MIT, and a core faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard University.With...
's and Anthony Forster's synthetic cell projects. As in the T7 example above, this favors a synthesis-from-scratch approach.
Key enabling technologies
There are several key enabling technologies that are critical to the growth of synthetic biology. The key concepts include standardizationStandardization
Standardization is the process of developing and implementing technical standards.The goals of standardization can be to help with independence of single suppliers , compatibility, interoperability, safety, repeatability, or quality....
of biological parts and hierarchical abstraction to permit using those parts in increasingly complex synthetic systems. Achieving this is greatly aided by basic technologies of reading and writing of DNA (sequencing and fabrication), which are improving in price/performance exponentially (Kurzweil 2001). Measurements under a variety of conditions are needed for accurate modeling and computer-aided-design (CAD).
DNA sequencing
DNA sequencingDNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
is determining the order of the nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
bases in a molecule of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. Synthetic biologists make use of DNA sequencing in their work in several ways. First, large-scale genome sequencing efforts continue to provide a wealth of information on naturally occurring organisms. This information provides a rich substrate from which synthetic biologists can construct parts and devices. Second, synthetic biologists use sequencing to verify that they fabricated their engineered system as intended. Third, fast, cheap and reliable sequencing can also facilitate rapid detection and identification of synthetic systems and organisms.
Fabrication
A critical limitation in synthetic biology today is the time and effort expended during fabrication of engineered genetic sequences. To speed up the cycle of design, fabrication, testing and redesign, synthetic biology requires more rapid and reliable de novo DNA synthesisOligonucleotide synthesis
Oligonucleotide synthesis is the chemical synthesis of relatively short fragments of nucleic acids with defined chemical structure . The technique is extremely useful in current laboratory practice because it provides a rapid and inexpensive access to custom-made oligonucleotides of the desired...
and assembly of fragments of DNA, in a process commonly referred to as gene synthesis
Gene synthesis
Artificial gene synthesis is the process of synthesizing a gene in vitro without the need for initial template DNA samples. The main method is currently by oligonucleotide synthesis from digital genetic sequences and subsequent annealing of the resultant fragments...
.
In 2000, researchers at Washington University, mentioned synthesis of the 9.6 kbp Hepatitis C virus genome from chemically synthesized 60 to 80-mers. In 2002 researchers at SUNY Stony Brook succeeded in synthesizing the 7741 base poliovirus
Poliovirus
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is...
genome from its published sequence, producing the second synthetic genome. This took about two years of painstaking work. In 2003 the 5386 bp genome of the bacteriophage
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...
Phi X 174 was assembled in about two weeks. In 2006, the same team, at the J. Craig Venter Institute
J. Craig Venter Institute
The J. Craig Venter Institute is a non-profit genomics research institute founded by J. Craig Venter, Ph.D. in October 2006. The Institute was the result of consolidating four organizations: the Center for the Advancement of Genomics, The Institute for Genomic Research, the Institute for...
, has constructed and patented a synthetic genome of a novel minimal bacterium, Mycoplasma laboratorium
Mycoplasma laboratorium
Mycoplasma laboratorium is a planned partially synthetic species of bacterium derived from the genome of Mycoplasma genitalium. This effort in synthetic biology is being undertaken at the J. Craig Venter Institute by a team of approximately 20 scientists headed by Nobel laureate Hamilton Smith, and...
and is working on getting it functioning in a living cell.
In 2007 it was reported that several companies were offering the synthesis of genetic sequences
Gene synthesis
Artificial gene synthesis is the process of synthesizing a gene in vitro without the need for initial template DNA samples. The main method is currently by oligonucleotide synthesis from digital genetic sequences and subsequent annealing of the resultant fragments...
up to 2000 bp long, for a price of about $1 per base pair and a turnaround time of less than two weeks.
By September 2009, the price had dropped to less than $0.50 per base pair with some improvement in turn around time. Not only is the price judged lower than the cost of conventional cDNA cloning, the economics make it practical for researchers to design and purchase multiple variants of the same sequence to identify genes or proteins with optimized performance.
In 2010, Venter's group announced they had been able to assemble a complete genome of millions of base pairs, insert it into a cell, and cause that cell to start replicating.
Modeling
Models inform the design of engineered biological systems by allowing synthetic biologists to better predict system behavior prior to fabrication. Synthetic biology will benefit from better models of how biological molecules bind substrates and catalyze reactions, how DNA encodes the information needed to specify the cell and how multi-component integrated systems behave. Recently, multiscale models of gene regulatory networks have been developed that focus on synthetic biology applications. Simulations have been used that model all biomolecular interactions in transcription, translation, regulation, and induction of gene regulatory networks, guiding the design of synthetic systems.Measurement
Precise and accurate quantitative measurements of biological systems are crucial to improving understanding of biology. Such measurements often help to elucidate how biological systems work and provide the basis for model construction and validation. Differences between predicted and measured system behavior can identify gaps in understanding and explain why synthetic systems don't always behave as intended. Technologies which allow many parallel and time-dependent measurements will be especially useful in synthetic biology. MicroscopyMicroscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...
and flow cytometry
Flow cytometry
Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and/or chemical...
are examples of useful measurement technologies.
Examples
Molecular cloningMolecular cloning
Molecular cloning refers to a set of experimental methods in molecular biology that are used to assemble recombinant DNA molecules and to direct their replication within host organisms...
is a method used frequently by geneticist
Geneticist
A geneticist is a biologist who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a researcher or lecturer. Some geneticists perform experiments and analyze data to interpret the inheritance of skills. A geneticist is also a Consultant or...
s to obtain large quantities of a particular strand of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. It involves shaping a selected piece of DNA and inserting it into the DNA of a bacterium called a plasmid
Plasmid
In microbiology and genetics, a plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA. They are double-stranded and, in many cases, circular...
. Once the alien DNA is inserted the bacteria is allowed to replicate
Replicate
Replicate may refer to:* In biology, replication is a process by which genetic material, a cell, or an organism reproduces or makes an exact copy or copies...
thus replicating the DNA that it contains. After replication is completed the copies of foreign DNA are separated from the plasmid. In this sense the bacteria becomes a cyborg because a foreign element is introduced and interacts with the bacteria.
The Sleeping Beauty transposon system
Sleeping Beauty transposon system
The Sleeping Beauty transposon system is a synthetic DNA transposon that was constructed to introduce precisely defined DNA sequences into the chromosomes of vertebrate animals for the purposes of introducing new traits and to discover new genes and their functions.-Mechanism of Action:The Sleeping...
is an example of an engineered enzyme for inserting precise DNA sequences into genomes of vertebrate animals. The SB transposon
Transposon
Transposable elements are sequences of DNA that can move or transpose themselves to new positions within the genome of a single cell. The mechanism of transposition can be either "copy and paste" or "cut and paste". Transposition can create phenotypically significant mutations and alter the cell's...
is a synthetic sequence that was created based on deriving a consensus sequence of extinct Tc1/mariner-type transposons that are found as evolutionary relics in the genomes of most, if not all, vertebrates. This enzyme took about a year to engineer and since its creation has been used for gene transfer, gene discovery, and gene therapy applications
Biosensor
Biosensor
A biosensor is an analytical device for the detection of an analyte that combines a biological component with a physicochemical detector component.It consists of 3 parts:* the sensitive biological element A biosensor is an analytical device for the detection of an analyte that combines a biological...
technology is another example of cyborg bacteria. One such sensor created in Oak Ridge National Laboratory
Oak Ridge National Laboratory
Oak Ridge National Laboratory is a multiprogram science and technology national laboratory managed for the United States Department of Energy by UT-Battelle. ORNL is the DOE's largest science and energy laboratory. ORNL is located in Oak Ridge, Tennessee, near Knoxville...
and named “critter on a chip” used a coating of bioluminescent bacteria on a light sensitive computer chip to detect certain petroleum
Petroleum
Petroleum or crude oil is a naturally occurring, flammable liquid consisting of a complex mixture of hydrocarbons of various molecular weights and other liquid organic compounds, that are found in geologic formations beneath the Earth's surface. Petroleum is recovered mostly through oil drilling...
pollutant
Pollutant
A pollutant is a waste material that pollutes air, water or soil, and is the cause of pollution.Three factors determine the severity of a pollutant: its chemical nature, its concentration and its persistence. Some pollutants are biodegradable and therefore will not persist in the environment in the...
s. When the bacteria sense the pollutant, it lights up and is then processed or amplified. In Australia, biosensors have been created to detect virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es, bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, hormones, drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s, and DNA sequences. In the future scientists hope to create chips that can sense toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
s such as environmental estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
s and warfare agents. Even more recently chemists at the University of Nebraska created a humidity gauge by using gold
Gold
Gold is a chemical element with the symbol Au and an atomic number of 79. Gold is a dense, soft, shiny, malleable and ductile metal. Pure gold has a bright yellow color and luster traditionally considered attractive, which it maintains without oxidizing in air or water. Chemically, gold is a...
plated bacteria on a silicon
Silicon
Silicon is a chemical element with the symbol Si and atomic number 14. A tetravalent metalloid, it is less reactive than its chemical analog carbon, the nonmetal directly above it in the periodic table, but more reactive than germanium, the metalloid directly below it in the table...
chip. With a decrease in humidity there was an increase in the circuit flow. One unique feature that separates the chip from the bioluminescent ones is that that after it has been assimilated the bacteria no longer needs to be kept alive for the humidity gauge to work.
Nanotechnology
Nanotechnology
Nanotechnology is the study of manipulating matter on an atomic and molecular scale. Generally, nanotechnology deals with developing materials, devices, or other structures possessing at least one dimension sized from 1 to 100 nanometres...
also has made advances by using cyborgs.. Researchers at the École polytechnique de Montréal
École Polytechnique de Montréal
The École Polytechnique de Montréal is an engineering school/faculty affiliated with the University of Montreal in Montreal, Canada. It ranks first in Canada for the scope of its engineering research. It is occasionally referred to as Montreal Polytechnic, although in Quebec English its French...
in Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
have attached a microscopic bead to swimming bacteria. Using a magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
machine (MRI) the researchers have been able to use the magnetic properties of the bacteria to direct it to certain locations. The bead has no purpose at the moment but researchers hope store drugs or other viral fighting agents inside so that it may be released at the directed location.
Opposition to Synthetic Biology
Opposition by civil society groups to Synthetic Biology has been led by the ETC GroupETC Group
ETC Group is an international organization dedicated to "the conservation and sustainable advancement of cultural and ecological diversity and human rights." The full legal name is Action Group on Erosion, Technology and Concentration...
who have called for a global moratorium on developments in the field and for no synthetic organisms to be released from the lab. In 2006 38 civil society organizations authored an open letter opposing voluntary regulation of the field and in 2008 ETC Group released the first critical report on the societal impacts of synthetic biology which they dubbed "Extreme Genetic Engineering".
Safety and Security
In addition to numerous scientific and technical challenges, synthetic biology raises questions for ethics, biosecurity, biosafety, involvement of stakeholders and intellectual property. To date, key stakeholders (especially in the US) have focused primarily on the biosecurity issues, especially the so-called dual-use challenge. For example, while the study of synthetic biology may lead to more efficient ways to produce medical treatments (e.g. against malaria), it may also lead to synthesis or redesign of harmful pathogens (e.g., smallpox) by malicious actors. Proposals for licensing and monitoring the various phases of gene and genomeGenome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
synthesis began to appear in 2004. A 2007 study compared several policy options for governing the security risks associated with synthetic biology. Other initiatives, such as OpenWetWare, diybio, biopunk, biohack, and possibly others, have attempted to integrate self-regulation in their proliferation of open source
Open source
The term open source describes practices in production and development that promote access to the end product's source materials. Some consider open source a philosophy, others consider it a pragmatic methodology...
synthetic biology projects. However the distributed and diffuse nature of open-source biotechnology may make it more difficult to track, regulate, or mitigate potential biosafety and biosecurity concerns.
An initiative for self-regulation has been proposed by the International Association Synthetic Biology that suggests some specific measures to be implemented by the synthetic biology industry, especially DNA synthesis companies. Some scientists, however, argue for a more radical and forward looking approaches to improve safety and security issues. They suggest to use not only physical containment as safety measures, but also trophic and semantic containment. Trophic containment includes for example the design of new and more robust forms of auxotrophy
Auxotrophy
Auxotrophy is most commonly defined as the inability of an organism to synthesize a particular organic compound required for its growth . An auxotroph is an organism that displays this characteristic; auxotrophic is the corresponding adjective...
, while semantic containment means the design and construction of completely novel orthogonal life-forms.
Social and Ethical
Online discussion of “societal issues” took place at the SYNBIOSAFE forum on issues regarding ethics, safety, security, IPR, governance, and public perception (summary paper). On July 9–10, 2009, the National Academies' Committee of Science, Technology & Law convened a symposium on "Opportunities and Challenges in the Emerging Field of Synthetic Biology" (transcripts, audio, and presentations available).Some efforts have been made to engage social issues "upstream" focus on the integral and mutually formative relations among scientific and other human practices. These approaches attempt to invent ongoing and regular forms of collaboration among synthetic biologists, ethicists, political analysts, funders, human scientists and civil society activists. These collaborations have consisted either of intensive, short term meetings, aimed at producing guidelines or regulations, or standing committees whose purpose is limited to protocol review or rule enforcement. Such work has proven valuable in identifying the ways in which synthetic biology intensifies already-known challenges in rDNA technologies. However, these forms are not suited to identifying new challenges as they emerge, and critics worry about uncritical complicity.
An example of efforts to develop ongoing collaboration is the "Human Practices" component of the Synthetic Biology Engineering Research Center in the US and the SYNBIOSAFE project in Europe, coordinated by IDC, that investigated the biosafety, biosecurity and ethical aspects of synthetic biology. A report from the Woodrow Wilson Center and the Hastings Center
Hastings Center
The Hastings Center, founded in 1969, is an independent, non-partisan, non-profit bioethics research institute based in the United States. It is dedicated to the examination of essential questions in health care, biotechnology, and the environment...
, a prestigious bioethics
Bioethics
Bioethics is the study of controversial ethics brought about by advances in biology and medicine. Bioethicists are concerned with the ethical questions that arise in the relationships among life sciences, biotechnology, medicine, politics, law, and philosophy....
research institute, found that ethical concerns in synthetic biology have received scant attention.
In January 2009, the Alfred P. Sloan Foundation
Alfred P. Sloan Foundation
The Alfred P. Sloan Foundation is a philanthropic non-profit organization in the United States. It was established in 1934 by Alfred P. Sloan, Jr., then-President and Chief Executive Officer of General Motors.-Overview:...
funded the Woodrow Wilson Center, the Hastings Center
Hastings Center
The Hastings Center, founded in 1969, is an independent, non-partisan, non-profit bioethics research institute based in the United States. It is dedicated to the examination of essential questions in health care, biotechnology, and the environment...
, and the J. Craig Venter Institute
J. Craig Venter Institute
The J. Craig Venter Institute is a non-profit genomics research institute founded by J. Craig Venter, Ph.D. in October 2006. The Institute was the result of consolidating four organizations: the Center for the Advancement of Genomics, The Institute for Genomic Research, the Institute for...
to examine the public perception, ethics, and policy implications of synthetic biology. Public perception and communication of synthetic biology is the main focus of COSY: Communicating Synthetic Biology, that showed that in the general public synthetic biology is not seen as too different from 'traditional' genetic engineering. To better communicate synthetic biology and its societal ramifications to a broader public, COSY and SYNBIOSAFE published a 38 min. documentary film in October 2009 http://www.synbiosafe.eu/DVD.
After a series of meetings in the fall of 2010, the Presidential Commission for the study of Bioethical Issues released a report, on December 16, to the President calling for enhanced Federal oversight in the emerging field of synthetic biology. The panel that facilitated the production of the report, composed of 13 scientists, ethicists, and public policy experts, said that the very newness of the science, which involves the design and construction of laboratory-made biological parts, gives regulators, ethicists and others time to identify problems early on and craft solutions that can harness the technology for the public good.
“We comprehensively reviewed the developing field of synthetic biology to understand both its potential rewards and risks,” said Dr. Amy Gutmann, the Commission Chair and President of the University of Pennsylvania. “We considered an array of approaches to regulation—from allowing unfettered freedom with minimal oversight and another to prohibiting experiments until they can be ruled completely safe beyond a reasonable doubt. We chose a middle course to maximize public benefits while also safeguarding against risks.”
Dr. Gutmann said the Commission’s approach recognizes the great potential of synthetic biology, including life saving medicines, and the generally distant risks posed by the field’s current capacity. “Prudent vigilance suggests that federal oversight is needed and can be exercised in a way that is consistent with scientific progress,” she said.
See also
- Angela BelcherAngela BelcherAngela M. Belcher is a materials scientist, biological engineer, and W.M. Keck Professor of Energy at the Massachusetts Institute of Technology in Cambridge, Massachusetts, United States. She is director of the Biomolecular Materials Group at MIT and a 2004 MacArthur Fellow.Belcher grew up in San...
- BioBrickBioBrickBioBrick standard biological parts are DNA sequences of defined structure and function; they share a common interface and are designed to be composed and incorporated into living cells such as E. coli to construct new biological systems. BioBrick parts represent an effort to introduce the...
- Bioengineering
- Biohacking
- Computational biologyComputational biologyComputational biology involves the development and application of data-analytical and theoretical methods, mathematical modeling and computational simulation techniques to the study of biological, behavioral, and social systems...
- Computational biomodeling
- IGEMIGEMThe International Genetically Engineered Machine competition is a worldwide Synthetic Biology competition aimed at undergraduate university students.- Competition details :...
- List of emerging technologies
- Registry of Standard Biological PartsRegistry of Standard Biological PartsThe Registry of Standard Biological Parts is a collection of genetic parts that are used in the assembly of systems and devices in synthetic biology. The registry was founded in 2003 at the Massachusetts Institute of Technology and resides in the Koch Biology Building. The registry contains over...
- Synthetic genomicsSynthetic genomicsSynthetic genomics is a nascent field of synthetic biology that uses aspects of genetic modification on pre-existing life forms with the intent of producing some product or desired behavior on the part of the life form so created....
- Synthetic morphologySynthetic morphologySynthetic morphology is a sub-discipline of the broader field of synthetic biology.In standard synthetic biology, artificial gene networks are introduced into cells, inputs are applied to those networks, and the networks perform logical operations on them and output the result of the operation as...
- Systems biologySystems biologySystems biology is a term used to describe a number of trends in bioscience research, and a movement which draws on those trends. Proponents describe systems biology as a biology-based inter-disciplinary study field that focuses on complex interactions in biological systems, claiming that it uses...
- Nucleic acid analoguesNucleic acid analoguesNucleic acid analogues are compounds structurally similar to naturally occurring RNA and DNA, used in medicine and in molecular biology research....
- Expanded genetic codeExpanded genetic codeAn expanded genetic code refers to an artificially modified genetic code in which one or more specific codons have been allocated to encode an amino acid which is not among the twenty/twenty-two found in nature.-Background:...
External links
- Transgenics & Artificial Biosystems Genbrain Biosystem Network since 1999.
- syntheticbiology.org community site
- ETC Group resources on Synthetic Biology
- Synthetic Biology Project Synthetic biology news, events, publications and more.
- Applied BioDynamics Laboratory: Boston University
- Handbook - Synthetic Biology for Beginners - CEMA, Srishti, Bangalore
- Hastings Center synthetic biology issue page contains research and resources on the ethical issues in synthetic biology.
- Synthetic Biology Engineering Research Center (SynBERC) A NSF-funded multi-university effort to lay the foundations for synthetic biology.
- Pier Luigi Luisi's synthetic biology group
- SYNBIOSAFE: Safety and ethical aspects of synthetic biology
- Ars Synthetica A multimedia forum for engaging specialists and non-specialists in an informed, ethical, and democratic dialogue on the emerging field of synthetic biology.
- Article on applications of synthetic biology
- Art& Synthetic Biology
- GenoCAD: a web-based open source CAD application for synthetic biology
- SynbioSS: The Synthetic Biology Software Suite. Open license software for modeling synthetic gene regulatory networks
- TinkerCell: A desktop CAD software for synthetic biology
- Biobuilder.org an educational website to engage and inform a wider audience of synthetic biology enthusiasts
- International Association Synthetic Biology
- Collection of newspaper articles on SB
- A review on Human Practices and Synthetic Biology
- The Centre for Systems and Synthetic Biology, India
Multimedia
- Creation of an artificial virus by a Brazilian University (UFPE) members: it can be the beginning of realization of a vaccine against AIDS.
- Public 'Long Now' Debate on Synthetic Biology between Jim Thomas and Drew Endy
- Video interviews with synthetic biology experts, NGOs and funding institutions
- Documentary Film on synthetic biology and its societal aspects (DVD)
- Synthetic Biology & Design – "Speculative Designer" James King presents his work at The Hastings Center, a nonpartisan bioethics research center
- Synthetic Biology- video of lecture by Steven Blanke, Professor of Microbiology at the University of Illinois, hosted by the Program in Arms Control, Disarmament, and International Security (ACDIS), November 19, 2009. Topics include: definitions and principles of synthetic biology; BioBricks; Internationally Genetically Engineered Machine (iGEM) competition; applications for commercial use, biosecurity; risk assessments; Biological and Toxin Weapons Convention; models of institutional governance.