Jul 27 2009

Evolving Useful Bacteria

Genetically modified bacteria are already a common and useful component of chemical production. Many drugs, food additives, and industrial chemicals are churned out by engineered bacteria in large vats. Bacteria are little protein and chemical factories and we put them to good use.

But engineering a strain of bacteria to do exactly what we want is laborious and expensive. Traditionally engineers have tweaked one or two genes at a time and then looked for the results. But the production of many substances by bacteria may be controlled by 20 or more genes, and so the permutations of various mutations are enormous – too many to test individually.

But now genetic engineers have developed a new technique known as MAGE – multiplex automated genome engineering. What they do is to essentially evolve bacteria with optimized or at least greatly improved production of the substance of interest. The technique causes bacteria to rapidly mutate – causing thousands of mutations and billions of different strains.

This technique allows us to do some amount of rapid evolution,” says Harris Wang, a researcher at Harvard Medical School, who led the project along with colleagues Farren Isaacs and George Church.

They then select for the strains that produce the most of whatever they are looking for. Wang and Isaacs use lycopene as an example. Conveniently, lycopene stains bacteria red, so they can just select the reddest strains. For other end products other markers will have to be used. For example, for some protein products genetic engineers have incorporated bits of DNA into the target gene that produce fluorescence, so that the cells that glow the most have the highest concentration of the target protein.

This technology has a great deal of promise, as does anything that makes it cheaper and faster for industrial development of new products and methods. In addition to speeding up the production of new drugs, it may help our quest for biofuels. Some scientists think that biofuels may be a solution to our dependence on fossil fuels. Biofuel crops can be homegrown and they are a renewable resource. However, if we use existing farmland and farm crops this will raise the price of food, and corn and other such crops are not efficient sources of biofuel – it is still debatable if they even produce as much energy as they consume.

Attention is therefore shifting to biomass that has a higher energy density, a higher crop density (more biomass per acre), is currently a crop waste product (like stalks) or grows wild (like switchgrass). The problem with these sources of biofuel is that we need to develop an industrial process that can convert the tough fibers into ethanol – in a massive and cost effective way. Economics and scale are the keys – if it costs too much to make the biofuel, it won’t happen on a large scale while gasoline is relatively cheap.

While there are many research programs going on right now, no one has developed a complete and cost effective industrial scale process for extracting biofuel from switchgrass or a similar source. One of the best hopes, however, is bacteria. If we can engineer a bacteria to eat the grass and produce some substance, like ethanol or something close to ethanol, that can then be easily refined into biofuel, we are off to the races.

Since optimization of yield and efficiency is key to the success of any such process, the MAGE technique may prove essential to the success of biofuels.

The MAGE technique is also interesting because it is a direct application of evolutionary principles. The process works by increasing diversity randomly through mutations and then selecting those bacteria that by chance have the desirable trait. This clearly demonstrates that the two step process of evolution – random diversity and selection – works.

Creationists have argued that evolution cannot work because random mutation cannot provide specificity and direction, and that selection cannot increase information because it is a negative process – it only removes information. This argument is nothing but a diversion from logic and reality, however. It should be obvious that mutations increase information and selection provides non-random specificity and direction.

In response to MAGE as an example of evolutionary principles, creationists are likely to argue that the MAGE technique allows for the inclusion of genetic mutations already known to be desirable into the mix – including introducing genes from other species. So the diversity does not have to be entirely random. But even when it is, the process still works. Also, the selection is artifical, not natural. This is an old objection by creationists to artificial selection as an analogy of evolution. This is a non sequitur, however – the analogy is that selection can drive non-random change in a randomly varying system. It doesn’t matter if the selection is artificial or natural, all that matters is differential survival.

By itself, of course, MAGE does not prove that evolution is true. No single line of evidence can do this. But is does support basic evolutionary principles with a practical application. Creationists often charge that evolution has no practical application, as if utility is a marker of scientific truth. Not only is this argument fallacious, it is factually incorrect.Creationists excel at being wrong in two or more ways simultaneously. At least they are good at something.

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