合成生物学

In 1978 the Nobel Prize in Physiology or Medicine was awarded to Werner Arber, Daniel Nathans and Hamilton O. Smith for the discovery of restriction enzymes and their application to problems of molecular genetics. In an editorial comment in the journal Gene, Wacław Szybalski wrote: "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" (Gene 1978, 4, p 181).

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 Repressilator [1] is one good example of such work. Michael 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 networks, ordinary differential equations, stochastic differential equations, and Master equations (in order of increasing accuracy). Good examples include the work of Adam Arkin and Alexander van Oudenaarden. See also the PBS Nova special on artificial life Nova.

Biological systems are physical systems that are made up of chemicals. Around 100 years ago, 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, Steven Benner's group at Florida, Carlos Bustamante's group at Berkeley, and Jack Szostak's group at Harvard are good examples of this tradition.

Engineers view biology as a technology. 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, produce energy, provide food, and maintain and enhance human health and our environment. 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 Tim Gardner and Jim Collins' pioneering work on an engineered genetic toggle switch, the Registry of Standard Biological Parts, and the intercollegiate Genetically Engineering Machine competition (iGEM).

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 refactoring, 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 lab's synthetic cell projects). As in the T7 example above, this favors a synthesis-from-scratch approach.

In addition to numerous challenging technical issues, the vast potential of synthetic biology also raises concerns among bioethicists about its possible misuse by rogue countries and terrorists (New Scientist, November 12, 2005). The invention of metals led to plows and sewing needles but also to swords and spears. The creation of nuclear physics led to cancer radiation treatment and nuclear weapons. The study of synthetic biology can lead to cures for malaria, which kills millions annually, but also could lead to a redesign of the smallpox organism to be used as a weapon for which there would be no current immunological defense. In depth knowledge about controls and containerization for such research must stay ahead of the experimenters. What society currently lacks is confidence that control and defense systems are more than adequate to address accidents and misuse of such activity. Some detailed suggestions for licensing and monitoring the various phases of gene and genome synthesis are beginning to appear. There's also an ongoing, comprehensive, and open discussion of societal issues online at OpenWetWare.