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Synthetic biology: Building machines from DNA

The views expressed are those of the author and are not necessarily those of Scientific American.


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Synthetic biology is a science that lies at the intersection of biology and engineering—and is therefore quite an intriguing subject for a microbiologist to venture into. The microbiologist is used to seeing cells as complex and exciting organisms to explore and DNA as the starting point at which to begin those explorations. Within the discipline of synthetic biology however the cell becomes a chassis in which to carry out engineering tasks, and the DNA the building blocks used to design intracellular machines. Although synthetic biology has been practised in different forms throughout the century, the recent increase in DNA synthesis technology development means that small genetic circuits are far easier and cheaper to make, making synthetic biology more appealing to microbiologists who want to create their own intracellular devices.

Definitions of synthetic biology vary, although there appear to be three main types. First is the "Registry" form of synthetic biology championed by (among others) Drew Endy and Tom Knight [1]. They worked on the principle that manipulatable biological parts should be standardised, to be used like nuts and bolts in machinery. This standardised approach is achieved by considering each gene, or useful piece of DNA as a brick, a "biobrick." Each biobrick can be stored on a plasmid, a circular loop of DNA that can be easily inserted into cells.

[Fig 1 – Biobrick Diagram taken from the registry of standard biological parts: http://partsregistry.org/Catalog]

On either side of the biobrick are specialised sites for molecules called restriction enzymes. These enzymes can cut the DNA out, and it can then be attached to other pieces of DNA, in a process called "Standard Assembly"

[Fig 2 – Standard Assembly Diagram taken from the registry of standard biological parts: http://partsregistry.org/Catalog]

By using these standard parts whole intracellular systems can be built up, for example to turn on a fluorescent protein in the presence of a dangerous pollutant such as lead, or arsenic. Viewing the DNA as simply boxes that can be joined and separated creates a higher level of abstraction to allow engineers and other non-biologists to create machines without needing to know biological details of the workings of DNA. This in turn allows more complex systems to be designed, such as biological amplifiers, oscillators, random number generators[2], and even biological camera film[3]. All the parts are stored in a biobrick registry (a giant freezer!) at the Massachusetts Institute of Technology and the details of each part can be found online (http://parts.mit.edu).

The second form of synthetic biology is more concerned with affecting the output of important biological molecules than with building intracellular machines. Many drugs, such as antibiotics, are formed from bacterial products and there is therefore a lot of interest in both increasing the production of these drugs and in tweaking the cells to produce slightly different variations of the antibiotics, to help combat bacterial antibiotic resistance.

As well as using partially-synthetic systems to improve drug production, these synthetic biology systems also allow further biological exploration of how antibiotic pathways work. Recent research produced a cell which contained only all the necessary genes for life, with none of the genes usually used for antibiotic production [4]; addition of separate antibiotic-production pathways into this cell could help to explore how these pathways interact and potentially how to encourage cells to activate pathways for new antibiotics. This is considered by some to be not ‘true’ synthetic biology as it doesn’t involve standard parts or large constructions, but as it consists of creating novel forms of life by purposefully manipulating the DNA towards a desired end, I think it counts as synthetic biology.

The third form, possibly the one most discussed in the media, covers the work done by Craig Venter—using gene synthesis to create entire genomes [5] which can then be inserted into living cell, creating what might arguably be called a synthetic cell [6]. Venter is also involved in research that aims to create a synthetic ribosome (one of the most important protein structures in the cell). Although not likely to be achieved in his lifetime, the end goal seems to be to make an entire cell created from man-made components. This work may not have as many immediately obviously uses other than a lab curiosity but producing these synthetic systems often leads to many important breakthroughs in important synthetic biology techniques.

As it gains more attention in the eyes of the public, synthetic biology is already becoming a cause of some discussion and concern. The ability to engineer living systems carries with it worries related to bioterrorism, genetic modification of organisms and the misuse of genetic material. The extent to which this is a worry increases as synthetic biology tools become more available and easy to use. At the moment this is more of a theoretical threat, as constructing biological machines can take many years of time and effort and is therefore not an immediate threat as from a terrorist point of view chemical explosions are far easier and more effective to work with. However as this is still a risk, both the EU (http://www.synbiosafe.eu/) and the U.S. [7] have specially funded research to look into just how much of a threat synthetic biology poses, and what measures might be best to retain as many of the benefits of the research whilst reducing misuse.

Manipulating genes also brings in issues of intellectual copyright over living organisms and DNA sequences. The Parts Registry which stores biological machines is open source, but not all researchers are going to want to put their creations into a fully open source system, especially those that have designed products for commercial purposes. Likewise many bacteria that have been designed to have for increased production of antibiotics or other metabolites have been patented as their use is often industrial. Although patents for genes is a controversial subject, the patenting of designed man-made DNA sequences is more clear, although it does raise important ethical issues of its own. If you patent a sequence of DNA for arsenic sensing, do you cover all biologically designed arsenic sensors, or just your specific DNA sequence?

Despite these concerns synthetic biology is an exciting and fast-moving field to get involved in. Research into the issues surrounding the field, and proper monitoring to involve misuse will become more and more necessary, but that should not stop synthetic biology from delivering many of the exciting new devices and machines that it promises.

References:

[1] Engineering BioBrick vectors from BioBrick parts Reshma P Shetty, Drew Endy, and Thomas F Knight, Jr

[2] Synthetic biology: Designs on life Erika Check

[3] Synthetic biology: Engineering Escherichia coli to see light Anselm Levskaya, Aaron A. Chevalier, Jeffrey J. Tabor, Zachary Booth Simpson, Laura A. Lavery, Matthew Levy, Eric A. Davidson, Alexander Scouras, Andrew D. Ellington, Edward M. Marcotte & Christopher A. Voigt

[4] Genome-minimized Streptomyces host for the heterologous expression of secondary metabolism Mamoru Komatsu, Takuma Uchiyama , Satoshi Omura, David E. Cane, and Haruo Ikeda

[5] Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome Daniel G. Gibson, Gwynedd A. Benders, Cynthia Andrews-Pfannkoch, Evgeniya A. Denisova, Holly Baden-Tillson, Jayshree Zaveri, Timothy B. Stockwell, Anushka Brownley, David W. Thomas, Mikkel A. Algire, Chuck Merryman, Lei Young, Vladimir N. Noskov, John I. Glass, J. Craig Venter, Clyde A. Hutchison, III, Hamilton O. Smith

[6] Creation of a bacterial cell controlled by a chemically synthesized genome. Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA 3rd, Smith HO, Venter JC.

[7] DNA synthesis and biological security. Bügl H, Danner JP, Molinari RJ, Mulligan JT, Park HO, Reichert B, Roth DA, Wagner R, Budowle B, Scripp RM, Smith JA, Steele SJ, Church G, Endy D.

[8] Synthetic biology: promises and challenges Luis Serrano

About The Author: S. E. Gould is a graduate student working as a research assistant in the pathology department at the University of Cambridge, having recently graduated from Cambridge as a biochemist. Her current research focusses on the design of intracellular sensors within bacteria, and she is currently applying for a PhD in similar fields. When not staring down a microscope of pipetting tiny amounts of liquid into clear tubes she can be found playing the flute, attempting to write fiction and trying the odd bit of yoga.

 

The views expressed are those of the author and are not necessarily those of Scientific American.






Comments 2 Comments

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  1. 1. tharriss 8:19 am 11/10/2010

    Interesting article, thanks!

    Link to this
  2. 2. Quinn the Eskimo 2:54 am 11/11/2010

    Okay, I get that. But, tell me, if they become aware of themselves can they vote? Shall we tax them?

    Will they be allowed on facebook?

    Examine this; it never ends. You build it, then you have to educate it.

    Link to this

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