Bacterial evolution can be accelerated with the MAGE technique to produce large numbers of favorable mutations (micrograph image of E. coli bacteria magnified 10, 000 times)
Bacteria are prolific replicators, and some species can replicate into the millions in just a few hours. Bacteria, in the functioning of their cellular and biochemical machinery, also just happen to manufacture some very useful chemicals and bio-active molecules. The microbes also mutate readily in response to environmental triggers, and these alterations can spread throughout the colony and confer adaptive traits, over time, onto the newer, variant population.
These attributes of bacterial life forms have been exploited in the biology lab (and in other industries) for some time, but generating genomic diversity in the lab has been challenging; inserting genes or entire genetic sequences into a cell’s nucleus (and DNA) can be done readily, but controlling or directing how exactly these hybrids mutate, is quite another thing. Further, new phenotypes (the main physical traits or properties) don’t usually happen fast or frequently enough for practical uses. But with a new technique called MAGE (Multiplex Automated Genome Engineering), bacteria are now being engineered (and “directed”) to perform these functions much faster and much more efficiently.
The new technique was first developed by synthetic biologist George Church of Harvard University and is a significant improvement over previous “directed molecular evolution” and in vitro techniques. Researchers at the Harvard Medical School, MIT, and GIT (Georgia Institute of Technology) recently announced great success in accelerating the evolutionary change in a species of bacteria (E. coli) using the MAGE technique. This enabled them to select mutations, or variants, that over-produced the important, anti-oxidant compound lycopene.
According to research team member Dr. Harris H. Wang: “It (MAGE) is similar in the goals of directed molecular evolution but the big difference is that it is evolution on the organism level, whether it be new functions or new metabolism. Traditional molecular evolution generally deals with a single gene or a single protein.”
Starting with a “complex pool of synthetic DNA”, the bio-engineers were able to target some 24 genetic components in a cellular pathway (called the DXP biosynthesis pathway) simultaneously, modify all 24 of them, and recombine these elements to the tune of 4.3 billion variants (and higher) per day. It took the researchers about 3 days to select out those bacteria variants with at least a five-fold increase in lycopene production.
(Dr. Wang explains the photo, right): “Here’s a picture of the cells that we engineered to make lycopene. The red ones are producing a lot of lycopene and the whiter ones not as much. The idea is that we can generate with MAGE a population of cells with many different variants [and] genetic constructs, some of which are better than others. Lycopene as you know is an antioxidant found in tomatoes and this is just a demonstration of the potential to turn a cell into a drug/fuel factory.”
These high-productivity, mutant strains could then be rapidly cultured to produce the desired compound in large, commercially viable amounts.
In an interview, this author asked Dr. Wang, about the foreseeable impacts/uses of this technique. “Ultimately,” said Wang, ” this is a new way of accelerating the evolution of the whole organism in a very directed fashion (i.e., controlled by scientist). This is going to be important in new cell based therapies, new cell based production of drugs, or, say, biofuels.”
Academic paper reference: (H. Wang et al, Programming cells by multiplex genome engineering and accelerated evolution, Nature, 13 Aug. 2009, published online 26 July 2009)
Top photo by Eric Erbe, digital colorization by Christopher Pooley, both of USDA, ARS, EMU.
Bottom photo: H. Wang
Correction note: The author of this article has corrected the previous misspelling of the MAGE technique (the word MAZE was accidentally used in the first draft)
About Michael Ricciardi
WRITER’S COMMENT:
With this and other bioengineering successes, we bring ourselves that much closer to becoming wholly conscious agents of “natural” selection in our own evolution.
So far, there seem to be no serious ethical issues emerging around the use of this technology in single-celled life forms. One may wonder, however, that our bio-engineering technology is also accelerating–at a pace ahead of our ability to recognize the (intentional/unintentional) consequences and repercussions of what we are able to do in a laboratory. Once we start identifying favorable phenotypes (and their corresponding genotypes), and are able to rapidly select and reproduce said phenotypes, it becomes easier to imagine using this technique to effect evolutionary change on a larger (multi-cellular) scale.
While the technology holds tremendous promise for bio-medicine (and even for bio fuels) , it will no doubt become a major issue at future Bio-Ethics symposia as MAGE applications find their way into other realms of human science, medicine and society. There is also the slight possibility of a MAGE variant escaping into the wild, reproducing (and possibly mutating further), and altering ecosystems.
As always, advancements in human knowledge and technology bring with them dangers and unintentional consequences. These are considered “trade-offs” with the beneficial results, and usually, laws and public debate follow these discoveries (and their implementations in larger commercial/scientific practice) in a perpetual state of “catch up”. It is this author’s view that bio-ethics organizations and commissions need to be more proactive in this field–balancing the innovation and medical value with long-term insight into societal repercussions–and that no such trade-off should be accepted without robust, informed, public debate.
M.R.