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Life Made to Order
Roland Piquepaille writes "When he was president of Celera Genomics, Craig Venter was the leader of the private project which deciphered the human genome. Now, he has another goal: create custom-made organisms -- one DNA letter at a time. 'Venter's objective is not merely to tweak existing life forms by inserting genes that confer specific traits -- the main tactic in conventional genetic engineering. Instead he wants to assemble an entire genome, DNA letter by DNA letter, putting together only the genes he wants: those necessary for an organism's survival and those that will allow it to carry out a desired task.' If successful, maybe in a decade, this could yield new sources of energy or novel drugs. Venter is not alone in this quest. Other institutions, private companies or universities, have similar efforts under development. Check this column for a summary of this eye-opening -- but quite long -- Technology Review article."
Craig Venter is propounding the vision. But the real science/engineering described in that article seems to be the following:
In mid-2002, researchers at SUNY-Stony Brook synthesized a 7,500-letter long Polio DNA sequence, converted it to RNA, then "combined that RNA with enzymes and other molecules in a test tube, and watched as whole polio viruses assembled spontaneously."
The complicated chemical steps used to synthesize the DNA are error-prone; errors grow linearly with the number of steps "so researchers typically limit fragments to fewer than 80 letters."
The Stony-brook researchers thus took two years.
A company called Egea Biosciences has a prototype machine, the device makes a mistake only once for every 10,000 DNA letters, or bases, a 100-fold improvement over conventional techniques that typically have an error rate of one in 100.
The CEO of that company "says the technology could be extended to yield in a matter of weeks highly accurate strands 100,000 bases in length--long enough to make a very simple bacterial genome."
That's what I got out of the article. And a recognition that there is a loose analogy to semiconductor manufacturing in there. The Venter name is useful mostly for hype as far as I can tell. Actually, setting a vision is really important so I should cut him some slack, but I more appreciated the tech details above which were buried in the middle of the article.
--LP
...involved in the creation of a living thing. An astonishing array of proteins, complex sugars, and lipids are all necessary for even a unicellular organisms to be viable. These aren't as easily assembled as nucleic acids, but they are just as requisite. The public focus inevitably tends toward DNA and RNA, especially by marketers such as Craig Venter, and especially when the story is being told to a non-scientific readership. The real story in biology is always more complex than the headlines would have us believe. Why can't these people make a real contribution to the world of medicine and figure out how SARS works.
http://tinyurl.com/4ny52
ctually, the irony of your statement is that we're going to need better nano-technology to complete the task.
No. Nanotechnology is completely uninvolved in this. These guys are chemists, biochemists & geneticists not engineers.
As enthusiastic as these companies are, the problems in intentionally constructing a DNA molecule letter by letter are huge: notably, if you screw up in one spot, you can have tremendous problems.
No. Making DNA base by base is not difficult at all, and has not been for many years. DNA synthesizers can churn out oligos of good purity of lengths into the 100s of bases. Need longer? Make ligatable overhangs and have an enzyme put them together, ligation techniques are trivial molecular biology. As for mistakes, of course they happen, but any scientist worth her salt would sequence it along the way. Remember that Human genome project thing? That was just a lot of DNA sequencing. The machine mentioned in the long article as a long seqeunce synthesizer is just a robotic version of a bench biochemist doing what i described.
Further, there's no "spell check" for them, using current methods. They wouldn't know they had a problem until they start letting it reproduce, only to find that they have an [apparently] inexplicably error, possibly making the organism unviable.
No spell check of making sequences? True, sort of. During the synthesis there isn't, but sequencing it post symthesis is absolutely trivial.
Whats needed is sophisticated enough nanobots that will be able to not only perform the construction of the DNA, but to "spell check" it by running up and down its length continually, comparing it against the desired pattern
Ugh!These are called enzymes. Nanobots as normally pictured (a little robot with arms and pincers etc etc) are just pure science fiction. This is one of the worst areas of pop science literature.
This project is simply a lot of molecular biology, nothing novel in the techniques. What's new is trying to design a genome by hand as opposed to letting nature do it. I am skeptical that 1. it will work (beyond copying known genes), and moreover, 2. it will be even close to what evolution can/has accomplished.
What got kind of mushed together in the articles is a totally different aspect, that of non-natural amino acids. Peter Schultz;s lab (which is just down the hall from me) has created a system where a bacteria can incorporate an amino acid that is not one of the twenty used in natural proteins. You can add amino acids with all kinds of novel chemical groups and see if you can evolve proteins/organisms to work better with this expanded toolkit. Pretty cool.
-Ted
-=-=- Quantum physics - the dreams stuff are made of.