Sunday, May 23, 2010

OK, it's alive!...

We get it.  The announcement of synthetic life (the jury is still out on this label) by bioengineering pioneer Craig Ventner has sparked more intensity in a debate already in long in progress.

[So before we go any further, the monster was not named Frankenstein. His name was The Monster.]

Having cleared up that particular personal obsession, what does this tiny little dot of bioengineering amount to anyway?
The experiment involved creating a strand of DNA as specified by a computer in a sequencing machine, and inserting it into a dead cell of M. capricolum, and then watching it revivify and express the artificial markers and the M. mycoides proteins. It really is like bringing the dead back to life.
It was also a lot more difficult than stitching together corpses and zapping it with lightning bolts. The DNA in this cell is over one million bases long, and it all had to be assembled appropriately with a sequencing machine. That was the first tricky part; current machines can't build DNA strands that long. They could coax sequences about a thousand nucleotides long out of the machines.
Then what they had to do was splice over a thousand of these short pieces into a complete bacterial chromosome. This was done with a combination of enzymatic reactions in a test tube, and in vivo assembly by recombination inside yeast cells. The end result is a circular bacterial chromosome that is, in its sequence, almost entirely the M. mycoides genome…but made from a sequence stored in a computer rather than a parental bacterium.
Finally, there was one more hurdle to overcome, getting this large loop of DNA into the husk of a cell. These techniques, at least, had been worked out last year in experiments in which they had transplanted natural M. mycoides chromosomes into bacteria.
The end result is a new, functioning, replicating cell. One could argue that it isn't entirely artificial yet, since the artificial DNA is being placed in a cell of natural origin…but give it time. The turnover of lipids and proteins and such in the cytoplasm in the membrane means that within 30 generations all of the organism will have been effectively replaced, anyway. [More]
And that was the simplest explanation I read, just for the record. (Yet another reason I avoided life-sciences).  I think it is a very, very big deal, and will eventually find its way into the realm of politics, albeit too late to really affect an explosion in innovation in synthetic life.  See also: GM crops. In fact, I'm still waiting for farmers to discover what Tea Partiers think about GMOs right now.  Throw in folks with religious objections to GMOs and you could throw a real wrench in "small government" politics.  The only way to stop this is more government regulation, right?

But this new field of creation or manipulation of living material hints at some real possibilities that could show up on the farm.
Synthetic biology, as the field of man-made biological components such as Venter's is called, is a promising new field that raises as much concern as it does excitement. It's basically genetic engineering writ on a larger, more profoundly amped-up scale. That process could generate valuable new species that can produce vast amounts of much-needed food or pharmaceutical products, and Venter is already at work on such projects. Collaborating with Novartis, he is building a bank of man-made versions of every known influenza strain so that if a new strain, such as H1N1, begins to circulate during flu season, vaccine makers can simply pull the appropriate synthetic segments off the shelf and begin the vaccine making process, cutting the months-long job of sequencing the appropriate strain down to a single day.
Working with Exxon, Venter's team is investigating ways to harness algae to convert carbon dioxide into a hydrocarbon source for biofuel on a scale that would finally make such alternative energy options worth pursuing. "No natural algae we know would do this on the scale needed," he says. "So we have to use a synthetic genome technique to either heavily modify existing algae or devise whole new ones." And the same strategy can be used to build organisms that can clean up pathogens in water or boost nutritional content in foods such as wheat crops. [More]
Regardless of the marketable products that emerge from this research I think corn (maize) will be an easy choice for acting as a vector or host if possible.  Having a long history of similar genetic modification, public and professional resistance would likely be lowest. With millions of acres - often wall-to-wall, isolation or at least dilution could be more feasible.  And our industry certainly has the infrastructure (plenty of white lab coats, etc.) to support such breeding.

I am not talking about the over-ballyhooed "farmaceuticals".  If Big Pharma develops say, a cancer vaccine grown in soybeans they are not going to pay a farmer to grow it on land rented from someone else.  Extremely high value crops will be grown on company owned land by company employees.

But it could be some other bug or biological product could be extracted during the corn milling process, for example and have a large enough market to prompt interest in the millions of acres of corn that could be doing double duty.  This is wild speculation, but I think the premise is sound. The end product must be something compatible with commodity production for any dollars to be showing up in our pockets.

At the very least, the idea of synthetic life sliding from science fiction to newspapers is to be noted.

[Update: Carl Zimmer has added his own commonplace brilliant touch to this story, noting that the minute the cell was formed, evolution took over and began to reshape it.
The scientists who produced the new synthetic cell copied the genome of a microbe, letter for letter, and then inserted the synthetic version into a host cell. To determine that their experiment worked, they needed a way to tell the genomes of their synthetic cells from the natural genomes that were their model. So they inserted “watermarks” into the artificial genome. These sequences of DNA (which spelled out the work of Joyce and others through the genetic code) sit in non-coding regions of the microbe’s DNA. As a result, these watermarks cannot disrupt any essential protein-coding genes or stretches of DNA that are vital for switching genes on and off.
It turns out that the genome of the synthetic cell is not identical to its original, even if you ignore the watermarks. Mutations slipped into its sequence during its synthesis. Yet those mutations caused no harm to the microbe, presumably because they didn’t disrupt an essential function encoded in its DNA. Once the synthetic cell came to life and began to grow and divide, it copied its entire DNA, including Joyce’s words. But as lovely as those words may be, and as important as they may have been to the scientists during their experiment, they mean nothing to the microbe. Every time an organism replicates, each spot in its DNA has a tiny chance of mutating.
In the growing colony of synthetic cells, now numbering in the billions, it’s almost certain that Joyce’s watermark has already been defaced by a mutation. The bacteria that carry these degraded versions of Joyce presumably do not suffer from these mutations, since the watermarks don’t matter to them anyway. So they can keep replicating.By contrast, the DNA in the really useful parts of their genome is changing very little over the generations, thanks to selection. [More]
Like glyphosate resistance, the implacable forces of evolution keep us changing and moving toward a future to be chosen by the rules we uncover through research such as this.]

No comments: