User:NKuldell/Q/A working page

Disclaimer: This page is a work in progress but it may be a good place for Reshma, Barry and I to collaborate. No one should consider these complete or authoritative.

Question: How is synthetic biology different from existing, related fields like genetic engineering and metabolic engineering?

In some ways, nothing. People have been rationally modifying genetic material for much of recorded history (via breeding and crosses). More recently, recombinant DNA technology has permitted the more deliberate combination of pieces of DNA from different sources. Such technology has, among other things, lead to the general availability of human insulin. Now, however, we have the additional advantage of full sequence information for many of the planet's organisms AND ways to make the genetic material from scratch. These two technologies of sequencing and synthesis are key enabling technologies of synthetic biology.

Genetic engineering has been focused on making relatively small changes to biological systems. For instance, introducing a new gene into an organism (like insulin). Synthetic biology seeks to start from a "blank slate" and ask, what can we make? Thus, instead of perturbing existing systems and organisms, we attempt to make new ones.

Synthetic Biology also places a greater emphasis on the *engineering* than genetic engineering. Fundamentally, engineering disciplines try to make use of standard components that can be assembled in different ways to construct novel systems. Thus currently, synthetic biology seeks to build the foundations for engineering biology. The power of such an approach is that it allows people to build upon each other's work to an extent not possible in other disciplines which are more focused on one-off designs (like genetic engineering and metabolic engineering).

Metabolic engineering can be thought of as a specialization of synthetic biology for the purpose of retooling cellular metabolism for human purposes. Synthetic biology also has applications in other areas like materials fabrication, energy production, information processing and more.

Question: Why is biology so hard to engineer now?

Currently there is a wealth of sequence information available but limited ways to make experimental use of it. Additionally, we have a good understanding of basic cellular activities but only a few approaches to predictably combine activities in creative and re-useable ways. Both imbalances may be rectified through synthetic biology, for example with inexpensive and fast methods for DNA synthesis and with improved foundational technologies for reusing genetic elements. Thus Synthetic Biology brings with it new risks and rewards. It will be easy and cheap to make something not seen in nature, which means it will be done by folks who haven’t had the technology of genetic engineering at their disposal.

Question: Who is doing the work today to help biohackers make something useful?

Answer:

Question: Some people may foresee a day when Synthetic Biology can build complex organisms from basic biological materials. Can simple viruses and primitive life forms already now be synthesized?

Viruses have been synthesized. Life forms, not yet. For example, in 2002 Cello, Paul and Wimmer reported the successful de novo synthesis of poliovirus (Science 297:1016), creating from raw chemicals an agent that could infect mice, albeit with a whopping dose relative to the natural virus that leads to infection. The authors described their efforts as “fueled by a strong curiosity about the minute particles that we can view both as chemicals and as “living” entities.” Other examples of de novo synthesis of viruses are the phiX174 bacteriophage reported in 2003 (PNAS 100:15440) and human influenza (Science 310:77) in 2005. Noteworthy are the speed with which these viruses could be made, a mere two weeks from raw chemicals to infectious bacteriophage in 2003, as well as the technology’s potential for dual-use (e.g. Nature 2006 439:266).

Since viruses replicate only in living hosts, they are not themselves alive. A minimal life form would require self-replicating nucleic acids and a synthetic chassis in which to house them. A front-runner for the former is RNA with catalytic activity, including self-replication as described in 2001 (Science 292:1319). For the latter, lab built- membrane vesicles to encapsulate RNA were described in 2005(J Am Chem Soc 127:13213), but these assemble only through directed manipulations of experimental conditions. Thus, it seems efforts to enclose self-replicating nucleic acids in some spontaneously assembling bubble are underway but, to date, only components of a lab-generated living cell have been reported (http://www.pbs.org/wgbh/nova/sciencenow/3214/01.html)

Question: What questions or applications are being addressed by Synthetic Biology that aren't being explored or built using other technologies?

Some synthetic biologists are combining genomic information and and synthesis technologies to re-write the genetic code from living creatures like computer programmers might want to re-write the code for your PC, annotating their changes and making each element of code more manipulable. Examples of this include T7.1, two genomes in one cell and Blattner minimal coli. Other synthetic biologists are engineering the metabolism of simple organisms like bacteria or yeast to make therapeutic compounds whose natural reservoirs are in short supply. Recent success in this effort is artemisinen. Finally, synthetic biology can also be a great option for regular, old fashioned biologists who might like to test their existing models by building them from the ground up. This is akin to efforts in chemical engineering that

Question: What are the perceived benefits of synthetic biology?

not sure this is appropriate ... but I thought it was important info?

Biology has several features that are difficult or lacking in other engineering mediums including

1. Biological systems can manufacture materials and chemicals on a very small scale.
2. Biological systems can evolve.
3. Most importantly, biological organisms can self-replicate.

These properties imply that biological engineering ought to yield novel systems capable of operations and behaviors not achievable by other methods. For instance, systems that can exist and interact with the environment (perhaps sense a toxin or pollutant) and respond appropriately (metabolize the pollutant into a nontoxic product).

Who is investing in this and what do they see as the pay-off?

Currently much of the investment in the field is from the venture capital community into startup companies (e.g. Codon Devices). Codon Devices' goals are "in the short term, product opportunities include comprehensive sets of biological parts for large-scale research projects, engineered cells that produce novel pharmaceuticals, engineered protein biotherapeutics, and novel biosensor devices. In the longer term, the company's core technology is expected to enable improved vaccines, agricultural products, and biorefineries for the production of industrial chemicals and energy." [cite] Synthetic Genomics, Inc., another startup by J. Craig Venter, believes "there are potentially limitless applications for synthetic biology/genomics, everything from energy to chemicals to pharmaceuticals. In the near-term, we think that synthetic genomics has applications in the areas of cleaner and more efficient energy production, specifically in the production of ethanol and hydrogen." [cite]

The European Union has also made research in the field of synthetic biology a priority with specific funding initiatives. pdf The purpose of this funding is to stimulate science and technology research in the EU. The nonprofit Bill and Melinda Gates Foundation has made significant investment in efforts by Jay Keasling and colleagues in synthesizing large quantities of the antimalarial artemisin . Their motivation is to solve critical world health problems. [cite]

Question: While their methods are different, the end results of synthetic biology and genetic engineering seem similar: new organisms that are not seen in nature. If that is true, does it follow that synthetic biology is not bringing substantially new risks onto the scene?

The risks and rewards are likely different. If synthetic biology is wildly successful then a 4-year old child could build something cool with biological materials, whereas genetic engineering as it’s currently performed requires good technical understanding of the project, and access to specialized resources such as a lab bench and reagents. In the future, novel biological systems may be built with limited know-how, on a minimal budget and with no requirement for a specialized facility.