28 June 2012

An Explosion of Experimentation in Synthetic Biology

The cost of both decoding DNA and synthesizing new DNA strands... is falling about five times as fast as computing power is increasing under Moore's Law, which has accurately predicted that chip performance will double roughly every two years. Those involved in synthetic biology, who often favor computer analogies, might say it's becoming exponentially easier to read from, and write into, the source code of life. These underlying technology trends... are leading to an explosion in experimentation of a sort that would have been inconceivable only a few years ago. _Technology Review
This rapid improvement in the tools of synthetic biology is making it much easier to re-program living organisms, and to eventually generate a wide range of entirely new creatures -- custom-made for specific purposes.
Among its many projects, [George] Church's lab [at Harvard's Center for Computational Genetics] has invented a technique for rapidly synthesizing multiple novel strings of DNA and introducing them simultaneously into a bacterial genome. In one experiment, researchers created four billion variants of E. coli in a single day. After three days, they found variants of the bacteria in which production of a desired chemical was increased fivefold.

The idea, Church explains, is to sort through the variations to find "an occasional hopeful monster, just as evolution has done for millions of years." By mimicking in lab experiments what takes eons in nature, he says, he is radically improving the odds of finding ways to make microbes not just do new things but do them efficiently. _TechnologyReview
It is only natural to devise ways of speeding up evolution. But synthetic biologists are not likely to remain satisfied within the confines of nature, regardless of the speed of evolutionary change.

The new breed of scientists in this field will want to colour outside the lines.
[James] Collins wanted to study cellular processes by constructing gene networks rather than taking them apart. As a first step, he built a biological toggle circuit. A toggle is a mechanism with two possible states—in the case of a light switch, on or off. In the switch he and his colleagues built from DNA, two genes next to each other in a bacterial genome both produced proteins when they were "on." But Collins set things up so that each protein would block production of the other—if gene 1 was on, it would keep gene 2 off, and vice versa. With the aid of chemicals or a thermal pulse, Collins could flip between the two states. The DNA toggle switch was analogous to an electronic transistor, able to store a single bit of information. It was also an engineered example of the kind of feedback loop that often determines whether cells grow, divide, or die. "The idea that you could build a circuit out of biological parts helped launch the field of synthetic biology," says Collins. The results were published in January 2000. Soon Collins's toggle was joined by an expanding list of DNA circuits, including biosensors, oscillators, bacterial calculators, and similar molecular gadgetry. Researchers even established a Registry of Standard Biological Parts: 7,100 different DNA structures are available to order. Scientists were excited by the idea that biology might be modular and predictable, like something made with Lego blocks or computer code. Many scrambled to found companies that they hoped would commercialize the technology to produce fuels, drugs, or other products.

...[George Church's] Warp Drive Bio... combines computer science, chemistry, and genetic engineering in ways that would not have been possible until recently. It aims to use ultrafast DNA sequencing and synthetic-biology techniques, some of which Church pioneered, to hunt for potential medicines by scouring the DNA of millions of environmental samples that drug companies have collected and stored over several decades. Warp Drive is, in effect, searching for genetic parts that nature has already programmed to make particularly potent, useful chemicals. Church's technology will be used to generate copies of those parts, incorporate them into bacteria, and optimize their performance. Then the bacteria can be used to produce chemicals that, if all goes according to plan, have new and interesting therapeutic properties.

... If Church and Collins are intent on creating new synthetic parts and bioengineering techniques, [Gregory] Verdine is hoping to use many of the same techniques to unwrap the mysteries of how nature does it. Over the decades, he explained to me, pharmaceutical researchers have collected and stored tens of thousands, and more likely millions, of environmental samples, including dirt and pond scum. The idea was to discover some potent chemical in these mixtures by dripping extracts onto cancer cells or into petri dishes of bacteria. But that process is laborious and subject to chance. Most drug companies have scaled back such research.

The answer, Verdine decided, was to search for DNA instead. Given the plummeting cost of DNA sequencing, it's now feasible to simply decode all the genetic material present in, say, a drop of pond water teeming with microörganisms. Verdine says many of the natural drugs that have already been identified have similar DNA signatures—clusters of genes that often occur together in a microbe's genome. The trick, he adds, is to scan the samples' DNA to locate familiar-looking clusters that might be recipes for synthesizing a natural product—ideally, an important one that hasn't been found before.

Once identified, the DNA sequences will need to be engineered into a bacterium so that the company can produce the chemical and study the potential drugs. This is where the synthetic-biology techniques developed by Church will be crucial: in transforming the code into actual compounds. "We use genomics and informatics to find a gene cluster. But that's an information unit," Verdine says. "We have to get the molecule. Synthetic biology involves coaxing the cluster into biosynthetic factories, which then produce the molecules. If we don't have the molecule, the cluster is useless." _TechnologyReview

It is a very competitive field, with potential payoffs for commercialisation easily into the billions of dollars, and higher.

It is difficult to find and properly train minds capable of spanning the vast conceptual distances between the molecular, the genetic, the cellular, the physiologic, the pharmacologic, and the business / economic / legal /ethical issues.

And that is the crux of the issue: What the best human minds can do, with the assistance of the best tools that they can conceive and create.

This is one area where the contrast between dynamists and stasists could not be clearer.

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Blogger sykes.1 said...

If biology wasn't the dominant science of the 20th Century, it will dominate the 21st Century.

Some quibbles:

(1) The clause,"an occasional hopeful monster, just as evolution has done for millions of years.", violates the modern understanding of evolution via natural selection. No modern biologist would accept it.

(2) Moore's Law ceased operation almost 10 years ago. If it hadn't, your laptop computer would be operating at speeds above 20GHz. It's operating at the same plateau we reached in the early 2000s.

Friday, 29 June, 2012  
Blogger Matt M said...

It may be time to go back and reread The Andromeda Strain.

Friday, 29 June, 2012  
Blogger Stephen said...

Perhaps someday we will produce humans twice as intelligent and live twice as long. It is definitely something to hope for.

Friday, 29 June, 2012  
Blogger J said...

They will not be humans.

Friday, 29 June, 2012  
Blogger J said...

They will be synthetic molecular robots.

Friday, 29 June, 2012  

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