First Successful Genome Transplant In Bacteria

eldavojohn writes "Researchers reported the first genome transplant from one bacterium to another, thereby transforming the species from M. mycoides to M. capricolum. The research, published in Science, shows that it is possible to achieve a success rate of 1 in 150,000 genome transplants in bacteria. While this may not seem like very good odds, it's actually a major step towards synthetic life, opening up the possibility of tailoring bacteria to our needs. The article mentions medical uses and fuel production as possible applications."

Re:

[sveard]

Please... everyone knows 20th century colleges were basically expensive daycare centers.

Obligatory

[Karl0Erik]

Well, I, for one, welcome our new, tailored, microscopic overlords.

A step forward, but questions remain

[rritterson]

While this work is a good step forward toward the ability to insert completely synthetic genomes into living cells, there are some questions left unanswered by the paper that demand answers before the technique can be widely adopted. First, the authors only speculate freely on how the mycoides genome made it into the capricolum cells. It's believed that perhaps two capricolum cells fuse around a mycoides genome, but no evidence to support this claim is given in the paper. Second, the authors do only a single PCR of a single gene to look for the presence of capricolum DNA in the supposed 'new' mycoides cells. This is not nearly enough testing, in my opinion, especially compared to the extensive testing they did on the cells in order to prove the mycoides DNA was present, in it's original genomic form, without insertions.

Until we know how the DNA got there and where the original DNA went, the technique will remain a laboratory curiosity and not something, for example, that can be used in any sort of medical fashion. Still, the paper is fascinating and raises some interesting philosophical questions about what constitutes the information belonging to a species.

Re:

[PineHall]

Even simple life is very complex. I am always amazed at how complex simple life really is. Your questions are very good questions that need to be answered. They may not be easy questions to answer.

Re:

[2names]

IT'S A BIRD!

No wait...IT MIGHT BE A PLANE!

Hold on...OH YEAH, it's AMBIGUOUS MAN!!!!

Re:

[stevied]

It's believed that perhaps two capricolum cells fuse around a mycoides genome, but no evidence to support this claim is given in the paper.

I haven't read the paper (not interested enough to pay £££ for it), but there was this in TFA: "They suspect that cell fusion may play an important role in mediating the transplant due to the optimal concentrations of fusion solution." I don't know whether they tried running the experiment multiple times with different concentrations (including zero) of this agent, but if so, a correlation between the concentration and the number of bacteria that survive the antibiotic would be circumstan

Re:

[rritterson]

That is, again, speculation on the part of the authors. In the paper, the authors only say they believe the cells are fusing because eukaryotic cells also fuse in the same medium, with again no evidence to support the claim. So, we don't even know for sure whether the bacteria are fusing, let alone whether the concentration they used is somehow optimal for fusion to take place.

Re:

[DerangedAlchemist]

Until we know how the DNA got there and where the original DNA went, the technique will remain a laboratory curiosity and not something, for example, that can be used in any sort of medical fashion. Still, the paper is fascinating and raises some interesting philosophical questions about what constitutes the information belonging to a species.

Actually this is useful as a biotechnology technique without knowing what's going on. Biochemists don't actually know how things like heat shock gets genes into cell either, although they have some theories. "It just works" is perfectly fine for a genetic engineer. Mix and screen for the ones that took up the genes it the method used currently anyway.

Knowing how thoroughly, to screen though and how often only parts of genomes are transfered will be important though. Maybe you would add multiple, dif

Full Science paper.... they did it right..

[tempest69]

http://www.sciencemag.org/cgi/content/full/317/583 8/632 [sciencemag.org]

The authors agreed that a single PCR wasnt enough, so they went with a hindIII digestion and an agarose gel run, to make sure that the pieces were all the right size, and nopt some funky recombination. They also managed a few southern blots to further ensure their results. AND they did 1300 Random Sequences (with luck a sequence can be read to 1000ish base pairs..), and IT ALL MATCHED.... 1.09 million base pairs all fit right...

So my point is that they did the work, made sure it was bulletproof, got accepted into a major journal. And sure they dont know the whole story of whats going on, but it doesnt matter, they DID IT, a full Genome transplant, with proper methods used to ensure its validity..

Storm

Re:

[mok000]

We hail our bacterial microlords.

Anyone else?

[MBGMorden]

Anyone else read this as "First Sucessful Gnome Transplant in Bacteria"? I mean I know they little guys are smart and useful, but that's not reason to be sending them to do the job of nanites :).

You misunderstood

[benhocking]

They were merely replacing KDE.

Yup, sure did.

[Wabbit Wabbit]

Thank you. I was about to post the same thing.

I think we need to step away from our screens for a while.

Re:

[Xtravar]

I guess this gives a whole new meaning to Mono !

Har har har har har!!!

Strong containment

[jshriverWVU]

Since this life can be synthetic, there's nothing in nature that is a natural antibiotic. So if there less benign aspects of the new bacteria, and it gets loose in the wild, it has potential to severely damage the ecosystem. Better to plan for the worse case scenario, but hope for the best.

Re:

[Silver Sloth]

Throw the switch, Igor!

Re:Strong containment

[TheMeuge]

What are you talking about?

The proteins made by this bacteria are still identical to the parent strain. The cell wall and membrane composition of the recipient cells also don't change. Furthermore, the makeup of all the daughter bacteria will be identical to the parent strain as well. There is nothing new about the daughter cells... and certainly nothing "synthetic" in the way you seem to understand the term.

However, in reference to the article, I wonder... given the ease of transforming bacteria with plasmids... or using recombination-based transduction with phages, what the benefit of whole-genome transfer is, other than to shorten the time required to transfer large blocks of genes.

Re:Strong containment

[jshriverWVU]

Agree, at least in respect to what the article did. But down the road if they start doing research on creating custom DNA strands (in essense synthetic life) because it wouldn't be mapped to an identical natural strand. It can potentially be bad. This can also be very good. If they can create a custom made bacteria that attacks cancer cells, or whatever possible health benefits can be made is good. Just making the point they need to make sure they keep the research contained, especially if they start making non-naturally occurring DNA sequences.

Re:

[ajs]

But down the road if they start doing research on creating custom DNA strands

What you're trying to describe and what this article are about are radically different things, to the point of having nothing to do with each other.

(in essense synthetic life)

That's a leap of a few orders of magnitude.

because it wouldn't be mapped to an identical natural strand. It can potentially be bad.

Your hypothetical that has nothing to do with this article has the potential to "be bad." Yes.

If they can create a custom made bacteria that attacks cancer cells

Seriously, just stop. You're now writing science fiction. As with much science fiction, your story might one day be possible, but today it has nothing to do with research that's being done.

How did the parent get modded up?

Brought to you ny the

[geekoid]

"Ignorance breeds fear" Dept.

Re:Strong containment

[Valar]

Well, except that wide spectrum antibiotics target whole categories of bacteria. What really matters is the type of cell wall, because that is usually what antibiotics disrupt. As long as the resulting bacteria has a cell wall like the ones in other bacteria (and I see no reason why they wouldn't be designed that way), then we will have no problems, especially if it is a gram positive bacteria.

Re:

[Bearhouse]

And how long before somebody designs a bug specifically to resist such antibiotics?

Re:

[ichigo 2.0]

I doubt it would be any worse than the bacteria that are evolving in response to our antibiotic usage.

Re:

[Bearhouse]

Indeed - but do we need any MORE variants of the blasted things?

Re:

[ichigo 2.0]

Well no, of course not. But understanding the genome will help us develop countermeasures to evolving threats. Auditing the genes to discover flaws and exploits, if you will.

Re:Strong containment

[Andy Dodd]

The bugs have been successfully designing themselves that way thanks to our good friend evolution.

If someone wants to create an antibiotic-resistant superbug, it would be much easier for them to start with existing antibiotic-resistant bugs and tweak them with existing well-established techniques.

The big news of this article is not that genetic material was transplanted, but that the *full and complete* genome was transplanted. To be honest, while it's an impressive feat, for 99% of the applications mentioned in the article summary, existing "partial genome" transplantation techniques are more than sufficient. People have been doing partial genome transplants with success for nearly three decades now - see http://en.wikipedia.org/wiki/Insulin#Timeline_of_i nsulin_research [wikipedia.org] .

Strong containment unneccessary

[DerangedAlchemist]

Nature has been much, much more successful than any rational design to create antibiotic resistance. All that stuff about abuse of antibiotics, like taking them for viruses, stopping part way through or stupid uses like for cattle feed to promote growth, creates antibiotic resistance incredibly rapidly. And bacteria share these genes across species very frequently, making it especially dangerous. As for the artificial life, it turns out that nature has already very finely tuned bacteria for their jobs.

Oblig

[n dot l]

I for one welcome our new formerly-M.-mycoides-but-now-M.-capricolum overlords.

Re:

[pla]

Since this life can be synthetic, there's nothing in nature that is a natural antibiotic.

That conclusion doesn't follow from the given premise.

A modern PC counts as 100% synthetic, but dropping it in the ocean will "kill" it quite thoroughly.

Now, if you mean that, in terrestrial life's 3-billion-year long arms-race, no other lifeform has come up with a substance that specifically targets this particular lifeform, I would agree. But that doesn't mean nothing can kill it, just that nothing has killed

Re:

[n dot l]

So if there less benign aspects of the new bacteria, and it gets loose in the wild

Eh? As far as I understand it we've taken one kind of already existing bacteria and turned it into another kind of already existing bacteria. There really isn't any new kind of bacteria here.

Re:Strong containment

[tloh]

There are several concepts that often get muddled in discussions of genetic engineering. A couple things that need to be clarified about your comment:

    In the context of this current example. A genome transplant simply puts an existing set of genes into a microbe that didn't have it before. It isn't synthetic, it is still natural in the sense that it isn't created by man completely from scratch. So existing antibiotic would still be effective if it can target the genome donor.

    Escaping containment is probably not as big a problem as most people think. The reality of the matter is that the principles of evolution works to our favor here. When we do this kind of genetic manipulation, we create something that "works" to our satisfaction. However the methods we use are always very messy and inelegant. A success rate of 1 in 150,000 is mentioned. In order to make the process work for us, we often have to put in extra genes that help us keep track of the bacteria but does nothing to help the microbe live and survive. Our handi-work can never stand toe to toe with nature's evolutionarily derived babies. *Those* guys have had millions(billions) of years to perfect and optimize the process of surviving (and more importantly competing) in the natural environment. Laboratory subjects like the ones mentioned in the article are grown as mono-cultures where you have bacterial medium, the microbe of interest and nothing else. They live like pampered socialites. You put them in the wild and they would completely out-competed by their natural counterparts who have better survival traits like more robust metabolic pathways to better utilize available nutrients or faster response to environmental cues. Within a couple of generations, our lab subjects would most likely be either out competed to extinction or be in such a low activity state as to be insignificant.

    So it is actually the reverse that you need to worry about. Our creation doesn't damage the ecosystem, it is the ecosystem that poses a greater danger to our interests. One of my professors gave a great example that nicely illustrates the situation. Not many people realized that without human intervention, corn can not grow. The food crop that we know as corn has been selectively breed over thousands of years from an ancestral weed that resembles wild grass. Left to itself, a corn field would simply shrivel and die because the plants have no way to disperse it's seeds. (The kernels can't jump out of the husk by themselves.)

    The thing is humans create/modify plants/animals/bacteria for specific purposes of which "natural" survivability is a very low priority. We grow corn primarily so that it can produce big meaty seeds for us to eat. But for that matter it also becomes the favorite food of many other organisms. Sure, we care about how much of the food intended for our stomachs end up in the bellies of crop pests, but the main purpose of growing corn isn't to make them vulnerable to crop pests, it is to feed us and ours.

So in conclusion, any handi-work of ours from the brilliant, but still learning minds of our smartest geneticists would more likely than not, *NOT* menace the natural ecosystem.

Re:

[blahplusplus]

"In the context of this current example. A genome transplant simply puts an existing set of genes into a microbe that didn't have it before. It isn't synthetic, it is still natural in the sense that it isn't created by man completely from scratch. So existing antibiotic would still be effective if it can target the genome donor."

Any intervention is necessarily synthetic, since the bacteria is just not going to transplant a genome on its own without out our intervention. Just because the structure is 'natur

Re:

[tloh]

Let me ask you a question:

When a person receives a heart transplant, do you now refer to the recipient as a "synthetic human" who has undergone a "synthetic procedure"?

I think you would be hard pressed to find anyone who would reply "yes". The word "synthetic" would be a very poor choice to identify any items referred to in this current context. In any case, it seems you're missing the forest for the trees here. The point is that if the genome came from *somewhere*, rather than out of *nowhere*, any anti

Re:

[blahplusplus]

The point your missing of course is the HISTORY of that particular slice or reality, that organism has a synthetic history (i.e. it would not have occurred without us mucking about).

Juts because I take a natural twig and glue it to a rock, does not make history of it's combination a naturally occurring phenomena.

Unless the bacteria transplanted a genome into itself, it is not a naturally occurring phenomena (in this context), it is ARTIFICIAL (in this context).

When a person gets a heart transplant he is usi

Re:

[tloh]

Well, "artificial" would certainly be a much more appropriate substitution for "synthetic". I guess you are entitled to your own opinion about what you want to call something. Technical jargon in any field can be irritating/frustrating. But I would strongly caution you to use different words to express yourself in different company. I am a lab technician on the staff of the Biotechnology program at the local JC. I just showed our discussion to a few of the instructors (my bosses) this afternoon. They'

Re:

[blahplusplus]

We were just misunderstanding one another that's all...

You were using 'synthetic' in one context, I was using it in another (since many words have different meanings based on not only USAGE in different CONTEXTS) we just got our contexts mixed up that's all.

As for your colleagues they're just being anal retentive, it's one thing to one perfectionistic accuracy it's another to have the social tact and not be so quick to run our mouths when we are just having a misunderstanding.

Remember each persons mind is a

Re:

[Starcub]

Our creation doesn't damage the ecosystem, it is the ecosystem that poses a greater danger to our interests.

Arrogant crap. It's unbelievable what passes for scholarship in modern times.

One of my professors gave a great example that nicely illustrates the situation. Not many people realized that without human intervention, corn can not grow.

C'mon now, what he should have said is that corn as we have it today wouldn't exist, and even that you couldn't be sure of ...with crows and whatnot... man need not be t

Re:

[tloh]

Arrogant crap. It's unbelievable what passes for scholarship in modern times.

I'm sorry my scholastic aptitude upsets you. However, I don't think it is arrogant to suggest that our meddlings in genetics are much more vulnerable to the power of the entire ecosystem than the other way around. Quit the opposite, I think it is very humbling to realize that mother nature can often take our very best effort and use it as asswipe.

C'mon now, what he should have said is that corn as we have it today wouldn't exist, and even that you couldn't be sure of ...with crows and whatnot... man need not be the source of the crop.

That's kind of self-evident, don't you think? I'm not sure what crows have to do with anything. But I'm guessing you might be referring to the possibility of

childhood songs

[wolfgang_spangler]

[singsong]
one of these 150,000 things is not like the others..
while they both would kill goats if they had their 'drothers...
one of these is different, can't you see...
without a cell wall it should be easy...
[/singsong]

I'd like to take this portion of the post to apologize...

First Success?

[weinrich]

What are they talking about? I successfuly transplanted one of my Gnomes from the side garden to the front garden just last week. I even have pictures to prove it! How can they claim to be the first?

Re:

[iggymanz]

GNOME pffft, wake us up when you've done a successful KDE transplant

de ja vu?

[mapkinase]

Team Claims Synthetic Life Feat by Zonk [slashdot.org], which refers to Last Updated: Thursday, 28 June 2007 at BBC [bbc.co.uk] which refers to pretty much the same paper.

more importantly...

[Tumbleweed]

This means they're one step closer to creating Dark Angel, which I think we can all agree, is vastly more important. :)

Re:

[ArhcAngel]

This means they're one step closer to creating Dark Angel, which I think we can all agree, is vastly more important.

I think they've already developed the beautiful woman who won't give you the time of day and can kick your ass.

Gray Goo!

[tedgyz]

Gray Goo! Gray Goo! Gray Goo!

Um, that would be "green goo".

[Spy der Mann]

Gray goo is a blob made of self-replicating nanomachines. Green goo is the biological version.

Little do they really understand.

[bradbury]

The problem with this news article is that most people hearing about it and commenting on it are clueless with respect to what it means and doesn't mean.

It means that someone walked into your house took all the old furniture out and replaced it with a whole bunch of different but similar furniture so that when you got home in the evening you could still sit down on the couch and watch TV.

So what everyone is going gaga over is the fact that the movers can take furniture out and replace it with different furniture. To be honest, I'm not that impressed. It has *nothing* to do with synthetic life, artificial life, etc. because they are *still* using the few hundred enzymes that nature had to evolve over billions of years. They didn't sit down and design a totally new basis for self-replicating systems that can survive in our "real" world and make a copy of itself. The hard drive in your computer is significantly more impressive. It has more parts and using a single command I can get it to copy itself. And *we* humans had to design every single circuit and craft every single part in it. Now *thats* something to be impressed with.

Re:

[decipher_saint]

If I replaced you every night with your clone implanted with identical memories would you be cool if you found out about it?

Human nature:
4. Fear
3. Anger
2. ???
1. Understanding

Re:

[bradbury]

I don't have a particular attachment to my current instantiation. A copy is a copy is a copy. And if it had really identical memories I don't see how he (I) would realize that he (I) was a copy. I do realize of course that there are people who don't happen to feel this way.

Re:

[Loconut1389]

Check for the dots under your eyelids...

Re:

[SpinyNorman]

The first wetware implementations of artificial life will of course be using nature's building blocks, but you have to start somewhere. What this work provides is an "test environment" for running the artifical DNA that Venter et al are designing.

I'm sure that later (maybe within our lifetime) we'll be able to design out own life forms completely from scratch, but rather ironically intelligent design really is the hard way to do it. Nature used the dumb brute force algorithm (cf Deep Blue playing chess) of

Re:

[bradbury]

No, no, no. You can of course start with "nature's building blocks" but you don't have to start there. Feynman and Drexler made that perfectly clear. There is "Plenty of Room at the Bottom". And taking a bunch of furniture out of one house and moving it into another house is not what I would classify as a brilliant achievement. Indeed, I suspect one would have to really work determining those cases where one cannot move the furniture from one house to another.

And it is not a given that the first wetwar

Re:

[SpinyNorman]

Sigh.

"I'm sure that later (maybe within our lifetime) we'll be able to design out own life forms completely from scratch".

I meant "of course the first wetware implementation of artificial life will use nature's building blocks" as a matter fact not of necessity. Craig Venter's "minimal life form" artificial DNA should be upon us in months and will of course be "executed" by inserting it into a living organism per this type of genome transplant technology. However superficial you regard this line of research

Re:

[bradbury]

The point would be that we have been engineering microorganisms with human designed and manufactured DNA, by your definition "artificial life", for decades, . Such exercises are done at hundreds of universities and companies on a regular basis. Once the sequences have been read (and over a thousand of them are now sitting in databases) the only real barrier to assembling a synthetic genome is cost. And this group hasn't even done that -- all they did was move a genome into a foreign house. And bacterial

Article is useless

[the_kanzure]

Most informative part:

The researchers explained that the transplantation method is simple in concept, though complicated to execute. First, the proteins were stripped from the M. mycoides LC cells, resulting in naked DNA that can be passed between cells. Then this intact DNA was incubated briefly with M. capricolum cells, soaking in a solution that caused the M. capricolum cells to fuse together. As two of these recipient cells fused, they sometimes encapsulated a donor DNA chromosome.

And then the citation:

Lartigue, Carole, Glass, John I., Alperovich, Nina, Pieper, Rembert, Parmar, Prashanth P., Hutchison III, Clyde A., Smith, Hamilton O., and Venter, J. Craig. Genome Transplantation in Bacteria: Changing One Species to Another. 3 August 2007, Vo. 317, Science.

Abstract:

Originally published in Science Express on 28 June 2007
Science 3 August 2007:
Vol. 317. no. 5838, pp. 632 - 638
DOI: 10.1126/science.1144622

Genome Transplantation in Bacteria: Changing One Species to Another
Carole Lartigue, John I. Glass,* Nina Alperovich, Rembert Pieper, Prashanth P. Parmar, Clyde A. Hutchison, III, Hamilton O. Smith, J. Craig Venter

As a step toward propagation of synthetic genomes, we completely replaced the genome of a bacterial cell with one from another species by transplanting a whole genome as naked DNA. Intact genomic DNA from Mycoplasma mycoides large colony (LC), virtually free of protein, was transplanted into Mycoplasma capricolum cells by polyethylene glycol-mediated transformation. Cells selected for tetracycline resistance, carried by the M. mycoides LC chromosome, contain the complete donor genome and are free of detectable recipient genomic sequences. These cells that result from genome transplantation are phenotypically identical to the M. mycoides LC donor strain as judged by several criteria.

The J. Craig Venter Institute, Rockville, MD 20850, USA.

* To whom correspondence should be addressed. E-mail: [e-mail]

But would it be too painful to actually add in relevant information from the published article? Not all of us know where to go get "Science" [sciencemag.org], nor do we have magical access [aaas.org]. Slashdot editors, if you would be so kind- stop accepting articles about papers behind paywalls. Some of us want to actually discuss the contents of these articles, the research methods, to look into what's actually going on ... not this hype that tells us nothing and wastes our time. ("You must be new!")

Anyway, genome transplantation means that maybe we can get the genome of our stem cells transplanted into bacteria. Just store lots of stem cell DNA, and then one day start the procedure to make the bacteria uptake the DNA and--- well, the current problem with this is that the human genome is much different from bacterial genomes, and so there will undoubtedly be way too many problems with the host bacteria, i.e. trying to make some of the proteins and biomolecules that actually causes self-destruction, but the concept/hope is still there.

BTW, the group that this article is about has been taking up way too much of our collective attention:
* Team claims synthetic life feat [slashdot.org]
* Venter Institute claims patent on synthetic life [slashdot.org]
* and now this.
And I should probably link over to this site [syntheticbiology.org].

Re:

[Anonymous Coward]

Genome Transplantation in Bacteria: Changing One Species to Another
Carole Lartigue, John I. Glass,* Nina Alperovich, Rembert Pieper, Prashanth P. Parmar, Clyde A. Hutchison, III, Hamilton O. Smith, J. Craig Venter

As a step toward propagation of synthetic genomes, we completely replaced the genome of a bacterial cell with one from another species by transplanting a whole genome as naked DNA. Intact genomic DNA from Mycoplasma mycoides large colony (LC), virtually free of protein, was transplanted into Mycopl

Re:

[mapkinase]

Just store lots of stem cell DNA

It seems like you need the whole shebang of the cell (epigenomics) as well.

Mycoplasma genitalium

[AcetylCoA]

"The scientists want to synthesize this genome, called Mycoplasma genitalium, using only simple chemicals." Did anyone else go "WTF!?!?" when they mentioned this name? Hmm.. although transplanting a naturally found genome to another similar bacterial cell doesn't seem like much, this actually means that once they're able to synthesize a minimum genetic sequence for basic cell function, like the one named above, they'll have a good chance of injecting the new genome into them and thus they will have just a

put my genome into Paris Hilton

[peter303]

One way or another :-)

Would this be like one of those "mind transplant machines" then?

The first steps

[c_woolley]

Great, so we have confirmed the first steps to bio-war through mutating germs...or we can hope that people actually use it for good intent. Of course, the road to hell is paved with good intentions.

This stuff does honestly scare me. The optimist in me realizes the benefits we can cultivate. The realist in me knows that this could honestly be far worse than a nuclear bomb.

I'd like to place an order for...

[xednieht]

...opening up the possibility of tailoring bacteria to our needs.

some bacteria to wash my dishes and pick up my stuff.

Bioshock

[Anonymous Coward]

OK, now the viral marketing for Bioshock has officially gone too far...

Re:

[Anonymous Coward]

That's bacterial marketing, you insensitive clod!

Mutation?

[Merritt.kr]

Am I the only one, that when I hear these things, thinks "Mutation" ? I can just see "We made a new bacteria to help us!" ... a few years later, "Oh no, the bacteria mutated and now it's going to wipe out 98% of the world's population!"

Re:

[JustNiz]

No you're not the only one.
This REALLY worries me too. Mankind is not ready to be trusted with this sort of power and responsibility. We have a terrible record of allowing big corporations to screw up nature for their short-term financial gain, while we pay the long-term price.

Re:

[cnettel]

Yeah, I suggest an immediate ban on yoghurt.