I've recently seen the term synthetic biology being used to describe research involving genetic modification of organisms. What is the difference between synthetic biology and genetic engineering?

Is it just a new term for the same thing, or is it something different? Does one of the two terms encompass the other?

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My understanding is that synthetic biology is genetic engineering 2.0. The difference is in the approach. Whereas genetic engineering projects are usually ad hoc, synthetic biology aims to apply proper engineering principles such as standardisation, modularisation, and reusability. Synthetic biologists create and use libraries of standard parts that are characterised, so they can be easily reused in projects. A part could be a gene, a terminator, a promoter, etc.

Synthetic biology also has greater ambitions. The focus is on creating whole systems/circuits of genetic regulation. This means there is a need for computational modelling and understanding of how biological systems work. In this aspect synthetic biology is a sister of systems biology a bit like synthetic chemistry (engineering) is a sister of chemistry (science).

You could of course argue that it's just a marketing ploy to invent a new name for something that is just the next step in genetic engineering, but the differences in approach are quite large and a new name signifies it.

With regards to synthesised vs. PCRed DNA: It doesn't really matter which you use in synthetic biology. However, cheap synthesis is one of the technologies that enable easier synthetic biology. The idea for the future is that you will be able to synthesise whole plasmids and chromosomes instead of having to "cut and paste" DNA. When that happens physical parts repositories will be obsolete, but they will remain crucial in silico. Cheap synthesis is nice, but doesn't make or brake synthetic biology.

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    $\begingroup$ I like this answer best - if you look at the partsregistry.org you can see there is a strong desire to put the components into an engineering framework that is more device like. $\endgroup$ – shigeta Sep 4 '12 at 18:41

It seems to me that the difference is mainly semantic, although the aims of synthetic biology are undoubtedly more ambitious than those of genetic engineering in, say, the 80s and 90s.

The Wikipedia page on genetic engineering has this definition of the difference:

Synthetic biology is an emerging discipline that takes genetic engineering a step further by introducing artificially synthesized genetic material from raw materials into an organism.

I must say that for me this doesn't really stand up to close scrutiny. To give just just one example from my own experience - for a long time now yeast geneticists have used PCR to make DNA for targetted gene disruption. This seems to me to fit the definition in the quote: the primers were made chemically and the PCR product was made in vitro using dNTPs as raw materials. (Admittedly the template DNA would be normally produced in vivo.) But I don't think we ever thought that we were doing synthetic biology.

Perhaps the term synthetic biology was intended to herald a new approach that would be more fundable?

I look forward to reading the responses to this rather cynical answer :)

  • $\begingroup$ I don't think they mean synthetic as in 'made in the lab using PCR', as for all genetic engineering PCR will be essential at some point (at least, that is how I interpret it). The term synthetic probably is used to refer to specific sequences of nucleotides that are not naturally formed (i.e. they are de novo, synthetic sequences). $\endgroup$ – Luke Sep 3 '12 at 11:42
  • $\begingroup$ I see what you are getting at, but wouldn't most mutagenesis experiments fit this definition? Conversely, if I was to synthesis a gene for a protein but changing as many codons as possible without affecting the amino acid sequence - what would that be? $\endgroup$ – Alan Boyd Sep 3 '12 at 14:16
  • $\begingroup$ Interesting point. 'Silent' mutations (those that do not affect the protein sequence) could still affect regulation of transcription - for instance miRNA binding or alternative splicing (this is very situation dependent of course, but I'm just saying that 'silent' mutations don't necessarily have no effect). With mutagenesis I would say it's genetic engineering, as there is no 'synthetic' element to the DNA modification, other than it is done under experimental conditions... an analogous experiment using a manufactured/custom sequence of DNA inserted into the genome would be 'synthetic' IMO. $\endgroup$ – Luke Sep 3 '12 at 14:56
  • $\begingroup$ ... however this is just my interpretation of things! I have not seen a concrete definition, so I may well be mistaken. Or indeed, there may not be a concrete definition, and this is quite subjective (like 'bioinformatics' vs 'computational biology'. People agree there is a distinction, but not on where the line is drawn). $\endgroup$ – Luke Sep 3 '12 at 14:56
  • $\begingroup$ PCR is not synthetic; although it involves biological synthesis, it has to start from a template. Synthesis as in synthetic biology involves artificial gene synthesis, i.e. starting just with a sequence on a computer and ending with biological sequence. $\endgroup$ – Rik Smith-Unna Sep 10 '12 at 1:52

They seem to be practically the same, with the exception of the goals. Genetic Engineering is the direct modification of the genes of an organism which results in capabilities being added or taken away. Synthetic Biology aims to modify the behaviors of an organism or integrate the behaviors of multiple organisms into a singular whole.

As is explained in Andrianantoandro E, Basu S, Karig DK, Weiss R. 2006. Synthetic biology: new engineering rules for an emerging discipline. Molecular systems biology 2: 2006.0028:

One useful analogy to conceptualize both the goal and methods of synthetic biology is the computer engineering hierarchy (Figure 1). Within the hierarchy, every constituent part is embedded in a more complex system that provides its context. Design of new behavior occurs with the top of the hierarchy in mind but is implemented bottom-up. At the bottom of the hierarchy are DNA, RNA, proteins, and metabolites (including lipids and carbohydrates, amino acids, and nucleotides), analogous to the physical layer of transistors, capacitors, and resistors in computer engineering. The next layer, the device layer, comprises biochemical reactions that regulate the flow of information and manipulate physical processes, equivalent to engineered logic gates that perform computations in a computer. At the module layer, the synthetic biologist uses a diverse library of biological devices to assemble complex pathways that function like integrated circuits. The connection of these modules to each other and their integration into host cells allows the synthetic biologist to extend or modify the behavior of cells in a programmatic fashion.

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    $\begingroup$ It's notable that in the paper's abstract the words engineer(ing) appear six times whereas synthetic appears just twice! The claim of the abstract is that synthetic biology is a new branch of engineering. The engineered constructs of synthetic biology will no doubt be achieved by use of DNA-based technologies. I stick by what I said in my answer: there is a difference of scope and ambition, but really there is nothing new; as the technologies have advanced and matured, so the possibilities have expanded. $\endgroup$ – Alan Boyd Sep 3 '12 at 15:23

In genetics engineering we use and manipulate natural genetic elements but in synthetic biology we make new gene elements and network.


In general:

genetic engineering = cutting and pasting existing DNA extracted from organisms

synthetic biology = chemically synthesizing DNA from scratch, which is used to create new genes and constructs from scratch. The synthetic sequences may not exist or may exist in nature.

  • $\begingroup$ I've been seeking the major achievements of synthetic biology. One that is frequently referred to is the production of the antimalarial drug precursor artemisinic acid in engineered yeast (Nature 440:940-3), a paper which has been cited hundreds of times. Upon reading this paper I find that everything that was done meets your definition of genetic engineering (and is what used to be called metabolic engineering). Please, can you point me to a research landmark that fits your criteria? $\endgroup$ – Alan Boyd Sep 9 '12 at 15:52
  • $\begingroup$ The parts registry, and BioBricks are key examples of synthetic biology. And Randy's is the correct answer, except that there's no reason to exclude sequences found in nature, as long as they are ab-initio synthesised. The clue is in the name... synthetic biology involves synthesised, not cloned, biological sequences. Synthetic biology is still a subset of genetic engineering. $\endgroup$ – Rik Smith-Unna Sep 10 '12 at 1:48

I am not a big fan of definitions and terminology in molecular biology, because biology is not physics, and things that we might describe and define change, as does our understanding of them. However, as this question has surfaced again after a number of years, it might be worthwhile giving a more recent example of synthetic biology, rather than just defining it. That way the reader can get an idea of what it is about.

I would say that:

Synthetic biology is a particular type of genetic engineering.


A reasonable definition of genetic engineering is given by Encyclopedia Britannica:

The artificial manipulation, modification, and recombination of DNA or other nucleic acid molecules in order to modify an organism or population of organisms.

So this could include making a single base change to inactivate a gene or introducing and expressing the gene for human insulin in, say, yeast.

The definitions of synthetic biology are more contorted, e.g. that from the Royal Society

Synthetic biology is an emerging area of research that can broadly be described as the design and construction of novel artificial biological pathways, organisms or devices, or the redesign of existing natural biological systems.


So why is the expression of insulin in yeast not considered synthetic biology? Basically because it lacks the complexity of a completely novel system. Consider the following description of an arsenic biosensor designed to test for arsenic in drinking water:

“Chris French at Edinburgh University led a team that turned the E. coli bacterium into an arsenic sensor by rewiring two genes. One gene senses arsenic and activates genes to pump it out of the cell; the other allows the bacteria to digest the sugar lactose, producing lactic acid. The rewiring involves putting the gene for digesting lactose under the control of the arsenic sensor. When arsenic is detected, the lactose-digesting gene switches on. The lactic acid it produces makes the water more acidic, which can be detected using a cheap pH indicator: if the reading is blue, the water is safe; yellow means it is dangerous.”

So they have engineered a completely new system with two different genes, which have been modified and their regulation co-ordinated (“rewired” in the article) in an original manner. And there is a tendency to embody some of the complexity into modules that can be reused by others allowing even more complex and sophisticated systems to be constructed.

You could say that the difference from insulin expression in yeast is only a matter of degree, but here the devil is really in the detail.


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