What is Synthetic Biology?
This quotation about the Molecular Biology revolution of the first part of the twentieth century sets the stage for synthetic biology.
It was a quarter-century ago that Watson and Crick, playing with cardboard cutouts and wire-and-sheet-metal models and sorting out the few controlling facts from a hotchpotch of data, elucidated the molecular architecture of the genetic material itself, the double-railed circular staircase of deoxyribonucleic acid. What has been learned in the years since is full of surprises, full of wit and beauty, full of the most gratifying illumination. The culmination is now approaching of the great endeavor of biology that has swept on for a century and a quarter—an achievement of imagination that rivals the parallel, junior enterprise in physics that began with relativity and quantum mechanics. Biologists' pursuit of complete and explicit understanding has begun to list the exact molecular sequences that encode the hereditary message, instruction by instruction; it has tweezed apart the springs and gears by which the message is expressed in the building of the cell, and the ratchets and pawls by which that expression is regulated; it has accustomed men to speak apparently without wonder of the structural transformations by which a single protein molecule, an enzyme, will break or build other proteins, or by which, for example, a molecule of hemoglobin will flex its broad shoulders and bend its knees to pick up oxygen.
To be sure, the discoveries have not produced the great practical payout that has repeatedly been anticipated for them. Biologists have no atomic power stations and no bombs to point to, or at least not yet. No baby has been cured of a congenital deficiency by insertion of a missing gene into its cells. There is no vaccine against human leukemia, not even a cure for hay fever. Though some of the rewards are at last imminent, most scientists have learned that they must speak guardedly and emphasize to laymen the gaps to be filled in.
The Eighth Day of Creation, Horace Freeland Judson, 1979
Hype and Substance
Like many new scientific fields (think nanotechnology), synthetic biology has been subject to a large amount of hype. Some even criticize it for not being anything new, but just a rebranding of other fields (recombinant DNA technology, metabolic engineering, etc.). There's not doubt that some of the flavor of the research question and new connections between forged between different fields are new. There are even some tremendous successes that can be claimed by the field of synthetic biology (full genome synthesis and engineering organisms to make certain new compounds). But, there are also many notable projects that turned out to be far more intractable than anyone imagined and have faltered partway through. An important aspect of this course will be analyzing and evaluating both types of outcomes and thinking about where synthetic biology will have the most impact in the future.
Very cool links giving the flavor of synthetic biology:
Types of Studies
- "The goal of synthetic biology is to extend or modify the behavior of organisms and engineer them to perform new tasks."
- "Synthetic biologists come in two broad classes. One uses unnatural molecules to reproduce emergent behaviours from natural biology, with the goal of creating artificial life. The other seeks interchangeable parts from natural biology to assemble into systems that function unnaturally." 
- Bottom-up assembly of genes, organelles and organisms.
- In contrast to traditional "top-down" genetic approaches that look for mutated versions of existing organisms.
- Ex:Re-factoring and re-writing genomes from scratch.
- Application of engineering principles to biology.
- Standardized parts that give predictable outcomes when put together in different combinations.
- Instantiating algorithms and problems from physics and math into biology.
- Ex: circuits, DNA computing, metabolic engineering
Program from Synthetic Biology Session for ASM 2012
ASM is the American Society for Microbiology.
- Evolutionary breakdown of engineered systems.
- Escape of recombinant organisms and synthetic genes from the laboratory.
- Debate over genetically modified foods.
- Misuse of tools for bioterrorism.
Recent Controversy in H5N1 Transmissibility Studies
Recent research has shown that reassortant viruses with the avian H5N1 protein HA (haemagglutinin) are transmissible among ferrets. It is unknown whether they are transmissible to humans. In order to prepare a presention to the public regarding the benefits of such research, researchers "have agreed on a voluntary pause of 60 days on any research involving highly pathogenic avian influenza H5N1 viruses leading to the generation of viruses that are more transmissible in mammals. In addition, no experiments with live H5N1 or H5 HA reassortant viruses already shown to be transmissible in ferrets will be conducted during this time."
They face an uphill battle in trying to convince the public that these studies are worth the risk, as synthetic biology is one of the most high-risk/high-reward fields. The risk of outbreak must be balanced against the greatly enhanced understanding of viruses that comes with such studies.
The Cartagena Protocol on Biosafety is an international treaty that addresses many of the concerns of biotechnology and synthetic biology. It formalizes and updates many guidelines in the tradition of the Asilomar Comference where concerns about recombinant DNA were first addressed by scientists.
Statement by the U.S. government: "The Protocol will enter into force on September 11, 2003. Although the United States is not a Party to the CBD and therefore cannot become a Party to the Biosafety Protocol, the U.S. participated in the negotiation of the text and the subsequent preparations for entry into force under the Intergovernmental Committee on the Cartagena Protocol. We will participate as an observer at the first Meeting of the Parties (MOP1), scheduled for February 2004 in Kuala Lumpur, Malaysia." http://www.fas.usda.gov/info/factsheets/biosafety.asp
Article 3. Use of Terms
(g) "Living modified organism" means any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology;
(i) "Modern biotechnology" means the application of:
a. In vitro nucleic acid techniques, including recombinant deoxyribonucleic acid (DNA) and direct injection of nucleic acid into cells or organelles, or
b. Fusion of cells beyond the taxonomic family,
that overcome natural physiological reproductive or recombination barriers and that are not techniques used in traditional breeding and selection;
9. Depending on the case, risk assessment takes into account the relevant technical and scientific details regarding the characteristics of the following subjects:
(a) Recipient organism or parental organisms. The biological characteristics of the recipient organism or parental organisms, including information on taxonomic status, common name, origin, centres of origin and centres of genetic diversity, if known, and a description of the habitat where the organisms may persist or proliferate;
(b) Donor organism or organisms. Taxonomic status and common name, source, and the relevant biological characteristics of the donor organisms;
(c) Vector. Characteristics of the vector, including its identity, if any, and its source or origin, and its host range;
(d) Insert or inserts and/or characteristics of modification. Genetic characteristics of the inserted nucleic acid and the function it specifies, and/or characteristics of the modification introduced;
(e) Living modified organism. Identity of the living modified organism, and the differences between the biological characteristics of the living modified organism and those of the recipient organism or parental organisms;
(f) Detection and identification of the living modified organism. Suggested detection and identification methods and their specificity, sensitivity and reliability;
(g) Information relating to the intended use. Information relating to the intended use of the living modified organism, including new or changed use compared to the recipient organism or parental organisms; and
(h) Receiving environment. Information on the location, geographical, climatic and ecological characteristics, including relevant information on biological diversity and centres of origin of the likely potential receiving environment.
- Andrianantoandro E, Basu S, Karig DK, and Weiss R. Synthetic biology: new engineering rules for an emerging discipline. Mol Syst Biol. 2006;2:2006.0028. DOI:10.1038/msb4100073 |
- Benner SA and Sismour AM. Synthetic biology. Nat Rev Genet. 2005 Jul;6(7):533-43. DOI:10.1038/nrg1637 |
- Array. .