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Microbe Processors
gpmap writes "Smart microbes are closer to reality than you might think, as described in an interesting article on Boston Globe Online. Ron Weiss, a Princeton biochemist, has already programmed E. Coli bacteria cells that release a fluorescent protein when they're exposed to certain chemicals. Now that a team at Stanford University has found a computer-based way to make cells react to any known chemical, the idea of weapons-detecting microbes looks even more promising. That is just one of the more modest applications of a remarkable new engineering discipline -- the science of programming cells. Imagine thousands of preprogrammed cells coursing through your bloodstream, checking cholesterol levels and patrolling for cancer. Or an army of bacteria powerful enough to suck the unwanted contaminant out of a whole lake, but smart enough to turn themselves off when no longer needed."
IMO, smart bacteria through genetic manipulation may be the quickest path toward all the goals that nantoech is attempting to achieve. After all, the cell is just such a 'nanomachine' with several billion years of refinement behind it.
So I wonder how much longer we'll have to wait until we have bacteria growing huge quantities of CNT's, or other small scale nanostructures.
...Cool technology that could make for a weapon. Kinda like a hammer.
And just to save some some of you the trouble:
Lets hope it's not used to wipe out ALL OF MANKIND.
The sky! IT'S FALLING!!!
Lets skip the rest of those sort of posts, shall we? 'Kay?
Fooz Meister
In response to the second comment by the poster about microbes that suck contaminants out of a lake and then shut themselves off, I would beg everyone to read 'Zodiac' by Neal Stephenson. He actually covers this exact scenario.
You have to remember two general differences between machines and organics: organics like to reproduce and organics benefit from an imperfect replication system. When you have a lifeform that can create millions of copies of itself within hours, even a 0.001% error rate makes for dozens of imperfect but potentially viable copies.
I have no problem with using organic-scale devices as solutions to problems, but personally I'd feel better if it was built from scratch with careful study put into the potential mutations. It's not a question of whether we can, it's a question of whether we should.
Very interesting concept, and amazing possibilities. Of course... this gives a whole new meaning to "debugging your code", or to finding a showstopper. I realize that this is a lot closer to biochemistry than it is to computer science, but nonetheless, using the programming metaphor suggests some worrying possibilities. Mainly, there is no chance for patches and bug fixes; it has to be right - 100% right - the first time. As another poster suggested, on a large scale even 99.9999% right isn't good enough.
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Microbe users guide:
Chapter II (detection):
If your urine is:
Blue: stop eating meat.
Green: time for your insulin shot.
Red: seek medical attention immediately!
What happens when the Bacteria decide its their lake? Next thing you know, they're making de-bigulators. I for one welcome our new microbial overlords.
Waiting for ad.doubleclick.net...
I want microbes that combine to taste like a twinkie or Oreo cookie, but after I swallow them, they dutifully form themselves into some form of dietary fiber that will not give me the runs (I'm thinking of things like Olean(TM) or olestra) nor will it constipate me. If they can do that, the world will be a wonderful place indeed.
It's not enough to bash in heads, you've got to bash in minds. - Captain Hammer
You have to remember two general differences between machines and organics: organics like to reproduce and organics benefit from an imperfect replication system. When you have a lifeform that can create millions of copies of itself within hours, even a 0.001% error rate makes for dozens of imperfect but potentially viable copies.
True, it is likely that they would evolve to do things their creators' didn't expect.
However, they would also be built using the same biological framework as all the life on this planet. The possibilities for negative reactions to existing biologic matter on this planet is staggering.
Perhaps we should stick to totally separate engineered constructs rather than DNA-based ones.
That, and Microsoft should be absolutely banned from tinkering in this area.
Imagine thousands of preprogrammed cells coursing through your bloodstream, checking cholesterol levels and patrolling for cancer. I already have thousands of preprogrammed cells coursing through my bloodstream patrolling for cancer. They are known as T cells. My liver handles the cholesterol.
"I'm so moist I'm sticking to the leather." -Kermit the Frog on The Late Late Show
Fred Smart-Microbe: (whispers) I told them we'll turn ourselves off when we're finished doing this!
Jim Smart-Microbe: Heh heh!
Combinatorial, baby.
So, if coli make an error in DNA replication 1/10^6 bases, and we make a huge guess at the probability of this error being somewhere important and doing something bad being 1/10^9, and we replace the cells living in the bloodstream once a year, and we have the safety features mentioned above, this becomes a very long sentence. There is little chance of something going wrong.
I'd still like to see how they are going to get these bacteria to live happily within the human body and not be noticed by the immune system, and not produce too much trash, and not grow uncontrollably.
An interesting idea, but ... give 'em a few grants and wait a few years.
...to see the interface between engineers of two different fields. I would have expected to see more knee-jerk "OMFG" posts speaking about the supposed dangers of this, and it's refreshing to see that there's few. It's also nice to see a post get into the nitty of nucleotides, Watson-Crick base pairing and the base pair wobble rules.
For those concerned about unleashing a transgenic bacterium into the wild that could have horrible consequences, consider the following (wrt. academic research): The E. coli used in research labs are most often "recombinant deficient," and viruses are most often "replication deficient." What this essentially means for E. coli is that genes coding for proteins that integrate foreign DNA into the bacterium's genome have been "knocked out" by one method or another (gross mutation, removing significant chunks of promoter sequence and coding sequence, etc). Plasmids carrying the ampicillin resistance gene that are subsequently transfected into the bacteria confer ampicillin resistance to those that carry it, and even replicate to a high copy number within the individual bacteria, but the ampicillin resistance gene does not get integrated into the host genome. Unless the culture is grown in a media that has a constant selection pressure (ampicillin), the bacteria tend to lose their plasmid. Keep in mind that Amp is heat labile and generally has a short half-life at 37 degrees C.
Likewise, replication deficient virus vectors have certain necessary virus sequences (certain packaging genes, promotor sequences, and long terminal repeats), but they also lack the crucial coding sequences that would give them the ability to become harmful and fully replicative. Example: A lentivirus (a subset of the retrovirus) vector can be made to be self-inactivating once it integrates into the host's genome. Additionally, for a researcher to make virions, they must transfect the virus vector into a transgenic "packaging" mammalian cell line that produces the viral coat proteins. Once you have enough of a virus titer, you use these virions to infect other cell lines (which are minus the genes that code for the coat proteins).
In a lot of cases, removing any coding sequences for proteins that facilitate DNA recombination in a host makes this sort of research quite safe when carried out under Good Lab Practice(tm).
While scientists are generally held closely to the ideals of the scientific method by their peers, there are protocols for minimizing risk (using recombinant minus host organisms), and these must also be followed. No scientist wants to be known throughout the world as the one who unleashed the monster.
With respect to the original story poster's comment about "turning themselves off:" It may have caused some confusion. The action of a cell responding to a chemical presence is usually through an inducible promoter system. The presence of a chemical catalyzes the recruitment of transcription mechanisms to the necessary location so they transcribe mRNA that codes for whatever the response is. In this case (as in indicator), it's the enhanced green fluorescent protein (EGFP). If you remove the chemical, the transcription machinery isn't mobilized to the promoter, and ultimately, EGFP isn't produced. Quite elegant. Do some searches for the lac operon or the trp operon if one is curious.
To end this and tie back into engineers of 2 different fields, a molecular bio grad student around our lab often wears the "Code Poet" shirt from ThinkGeek. I tend to think it's as in context as in CE/CS, wouldn't you? DNA is code of the most ancient sort. After looking at lines of ATG GTC CCA CGT CAC... for a while, one could liken it to assembler.
We haven't figured out our compiler fully, though.
Cheers!
-- I'd say your post was about 3 monkeys, 18 minutes.
What about Oreo-flavored yoghurt?
for the tip on Carb media/plates. We use it as much as any other selection media, although it's more than twice as expensive.
;)
Certainly, there are strains that are RecA pos, just as there are strains that express Tet and Cam resistance on their F' episome. I guess my point was more that there are such methods in place as to mitigate risk when working with engineered vectors. RecA is simply one layer of protection, and RecA- strains are used when it's needed.
As for curing a strain of a plasmid, I've never tried it directly, although you'll certainly lose your F' plasmid if you grow XL1-Blues without Tet.
I'm curious as to how you've accidently swallowed E. coli while doing lab work, though...multiple times? I can't think of a single time through all of the electroporations, ChemComp protocols, transformations, platings, yadda yadda that I ever got the pipette tip close to my mouth.
Good luck with your research, btw.
-- I'd say your post was about 3 monkeys, 18 minutes.
I don't like using carbenicillin either. Way too spendy and I seem to remember it being difficult to dissolve? Like when I make stables I don't like using G418 - puromycin being cheaper and faster.
Years ago I worked in a prokaryotic lab and we used all sorts of coli strains - I remember the first time I tried doing qiagen minipreps on an endotoxin expressing strain. Ok, so now I'm getting nostalgic. Now I'm in a protein biochem lab doing cancer-related stuff.
ps, e.coli in LB tastes nasty. salty and sour and quite a bit like it smells.
Let's hope that Microsoft isn't programming these bacteria...
Ever notice how fast Windows runs? Neither do I - get Mac OS