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An On/Off Switch for Genes
Jett wrote to us with a
report on some of the latest work being done in genetic theory. Scientists have made progress in being able to turn genes on and off at will, which is a critical step towards creating systems that will do what you want to them. This "toggle switch" can be triggered by either a specific chemical or a thermal rise. Nanotechnology is an area of convergence here as well - you can imagine the need for the ability to turn off some of your living nanites when unneeded.
The dream of obsessed anime fanboys everywhere. I wonder if this would also work for hair?
Really now, tampering with biological genes which have withstood thousands of years of evolution may destroy large sections of our world. It's no joke - imagine if they "switched off" the gene that makes us violent. We'd be completely defenseless - we wouldn't respond to violence, and hence the few genetic mutants that emerged would quickly dominate. Oh joy. How about this - make everybody intelligent. That's not such a bright idea either. With intelligence comes and increased desire to alter existing social structures. Get enough entropy stirred into the pool and the whole thing collapses into anarchy.
How many "good ideas" are out there by well-intentioned people? How about we turn everybody into "super" humans with fast reflexes, strong muscles, and longevity? Sure.. that'll only spawn a deep chasm between the genetic haves and the have-nots and might very well spark a war.
There are very serious and very dire decisions to be made with such technology. I hardly think such decisions belong in the hands of people making these decisions. We simply are not at the point socially or otherwise to start tinkering with human genetics. Understanding is one thing, modification is quite another!
Press release
Subject: Gilligan Nanite Processor
Release Day: Jan 19, 2004
After a long period of secrecy TransMetaTag Corp. finally announced the new Gilligan processor.
The new revolutionary processor uses nanites as it's core, translating Itanium instructions on the fly through a process known as "Gene Morphing". The nanites reorder and translate the instructions by pushing electrons through the right Gates at amazing speed.
"It was a breakthrough in nanotechnology that made this new design possible", says Linus Torvald Jr., "without the ability to turn them off, we could have never achieved our amazingly low power requirements".
Hemos could not be reached for comment.
Here's the info:
DNA Computing : New Computing Paradigms (Texts in Theoretical Computer Science)
by Gheorghe Paun, Grzegorz Rozenberg, Arto Salomaa, W. Brauer (Editor)
A few people emailed me asking about this book, I figure this is a good time to post it for all to see... its a very good book and after reading it you'll realize this is a really nifty thing for DNA-based computers.
Oh, and NO DNA knowledge is needed to read this book, I knew bothing going in, now I feel like I could do the stuff in my basement if I knew how to get DNA out of a living cell or how to synthesize it...
Esperandi
Inducible expression systems for research use have been around for a while. Judging by the MSNBC article, this is one is novel because, once induced, it stays induced.
o nline/
:-).
However, it's not really correct to think of (most) genes as being "on" or "off"; they are transcribed at a variable level depending on the local concentrations of one or several promoter proteins. The analog networks formed from these elements exhibit a variety of interesting nonlinear behaviors (of which switching is just one example) which help ensure that, for example, your cells divide at a rate just fast enough to replace their dying neighbors and maybe grow your body a bit -- but no faster.
We need to perturb these networks in order to understand them, but knocking out a gene or overexpressing it 1000-fold is like using a nuclear blast to twiddle the current in a sensitive circuit. Our lack of fine control over gene induction is one reason that dissecting gene networks is so hard.
Of course, there are other problems: biological control happens at the RNA [1] and protein [2] levels, not just the gene transcription level. We've got considerably better tech [3] for observing gene transcription than for watching proteins, but it's the proteins (especially the ones that bind to transcriptional promoters) that do the real work. Also, our analytical toolkit for network identification works great for linear systems but isn't so hot in the presence of nonlinearities and feedback.
For more information on how to analyze biological networks, see e.g. the proceedings of the latest Pacific Symposium on Biocomputing at
http://www-smi.stanford.edu/projects/helix/psb-
[1] RNA levels can be controlled not just by tweaking the transcription rate but also through selectively degrading mRNA's and by alternative splicing-out of introns to produce different transcripts.
[2] Proteins can be translated from mRNA and later degraded at variable rates. More importantly for fast responses, they can turn each other on and off through kinase activity (e.g. by adding and removing phosphate groups from particular sites in the protein).
[3] The latest and greatest tech for measuring gene transcription is the cDNA or oligonucleotide microarray. For example, see the GeneChip at www.affymetrix.com. Please don't ask me how quantitatively reliable these methods are -- the answer would only depress you
Disclaimer: I have not read the original article, merely the crappy MSNBC piece stuffed with "factoids". how thoroughly was this tested and how good is the understanding we have of the systems involved I would imagine that one of the benefits of this work is that it will allow investigation of complex phenotypes. Many phenotypes are controlled by several genes operating in weird regulatory networks. The ability to switch on and off bits of this network merely by dumping in chemicals would be great. A different specific switch for each gene in the network. What happens when gene 1 is on and 2,3,4 are off etc. So, this could allow us to understand better what is happening with developmental defects, homeostatic defects etc What will it end up costing? If we live in an unethical , immoral society which prizes other goals than human dignity and freedom, well then, probably those two latter will go by the board when a technology that can affect them that also happens to be profitable turns up.Change the system, don't kill the science!
I suppose the breakthrough lies in the ability to synthesize a genetic switch in vitro. As sensors, they will be a lot less invasive than mechanical and electronic sensors. But their implementation still faces the same barriers common to all gene therapy: delivery systems and persistence. We have yet to perfect a method for stably integrating a synthetic chromosome into a eukaryotic cell, and transfection of small pieces of DNA is usually temporary because they will rarely integrate with the genome.
In terms of revolutionizing genetic engineering, if we do figure out how to insert such a switch into a pre-existing gene, we'll only be able to solve autosomal dominant disorders, and only the ones that are due to dominant negative effects, like some forms of osteogenesis imperfecta, where a bad copy ruins the good copy too. Other autosomal dominant disorders are due to haploinsufficiency, meaning that one good copy isn't enough for the job, so turning off the bad gene won't help. Autosomal recessive and sex-linked disorders cause problems because there are no good gene products, so turning off genes won't really help, and there isn't anything to turn on. In any case, if we were to understand such a gene well enough that we could confidently install a switch, it would just be easier to replace the bad gene with a good copy than inserting the switch.
It would be interesting to construct a computer from genetic switches, however. Such a switch wouldn't have to only represent 0 and 1.
and I can tell you that this story is not in any way 'new' news. Maybe the nano blurb is a new idea for this technology, but the idea of turning on and off engineered genes at you're discretion is not.
The system they are referring to is known as a tetracycline responsive promoter. A commercially kits for this purpose are available here.
Having used the system, I can tell you it does not work very well. A better system is located here and an even newer system here. I rarely post here, but I have noticed that most of the pieces on biologically related topics that make it on /. are not well researched on the poster's part. When I think about it, the majority of news and pseudonews sites on the web and in the traditional media fail miserably when producing stories about science in general and particulary regarding biology.
Yo