Field of Science

Craig Venter's Synthetic Genome

ResearchBlogging.orgI'm taking a miniscule break away from revision to quickly write my thoughts about the news thatt Craig Venter has finally made a 'synthetic cell' or, as Psi Wavefunction more correctly pointed out, a synthetic genome inside a normal cell. It's quite a landmark for synthetic biology; not only has an entire genome been constructed from scratch, but it's also able to replicate and make new bacteria with the same genome.

What the researchers did was to synthesise an entire genome, that is all the DNA present in the bacterial species Mycoplasma mycoides (1.08 Mbp - mega-base-pair for anyone interested), by making lots of 6 kpb (kilo-base-pair) pieces and splicing them together in yeast. They then had to carefully get the completed genome out of the yeast, and put it into an empty (i.e containing no other DNA) M. mycoides cell. The resulting bacterial cell contained only synthetically made DNA, and was capable of surviving and replicating quite happily.

Above is a scanning electron microscope picture of the dividing cells

Probably the first thing to notice about this is despite it being pretty damn impressive, it's not exactly the creation of new life. It fact, I'm not sure I'd say it's even the creation of life, just the creation of a working genome. And despite what Richard Dawkins might think you need a lot more than just a working genome to be defined as life, especially life as complicated as a bacteria. What's been achieved here is sort of the bacterial-genome equivalent of in vitro fertilisation; the DNA has been synthetically made, but it's been put into a working bacteria, containing all the proteins, lipids and other molecules that are essential for life.

I'm certainly not putting this down, it's an amazing piece of work which makes my excitement over getting a 6kb gene synthesised over the summer seem very childish. But heralding it (or indeed condemning it) as 'Scientists create life' is a little over the top. DNA is, if anything, one of the easiest things to make in the cell, given it consists of different rearrangements of four base-pairs, all in a long string. Small bits of DNA have been synthesised for a while, but as yet, no one really has much of a clue how to synthesise bacterial cell membranes, let alone how to get them to synthesise and replicate themselves.

This is the genome that Venter built. The text in the middle shows the process in full. The little letters around the edge (BssH II etc) show sites for restriction enzymes which are used to cut the genome into little pieces for analysis.

One of the questions that always comes up whenever synthetic biology is mentioned is "how safe is it?" after all, this is a man-made genome going into a bacterial cell. Surely you could make another, more dangerous genome, and put that inside a bacteria and then use it to cause destruction, or a B-movie sci-fi plot? I suppose the risk is always there but in all reality, there are much better, cheaper and faster ways to ensure destruction happens. It took Venter's team six years to get this whole thing completed and working and while it's true that the process is only going to get faster I don't see it getting any quicker than rummaging around under the sink and coming up with enough ingredients to explode. Last summer it took around one and a half months to get my 6kb gene sequenced, and two months of work completely failing to make two very small mutations in another 2kb gene. There are people who fiddle around in their garages doing synthetic gene cloning, but there appears to be a pretty non-existent overlap with terrorist activity.

So this is a big step for genomes, but a tiny step towards a fully synthetic cell. Getting the full genome was a matter of time, patience, a large supply of base-pairs, plenty of money, and doing something clever with the base-pair methylation. Trying to make a synthetic membrane requires understanding how the things work first. Every new organism starts its life in a little cocoon of useful proteins, internal-membrane structures and little filaments which help to organise DNA expression even as the DNA controls their production and regulation. Putting new DNA into this pre-existing system is something that organisms do every time they replicate. Making the whole system from scratch is something that's never actually been done before, given that each generation has at best just tweaked the design a little from whatever the original cellular background was - probably just a quick scattering of proteins surrounded by a couple of glycolipid layers. Over the billions of years it's had to evolve, this has created a mysterious and highly complex system which would be incredibly difficult for a research to attempt to replicate.

I bet Venter's labs are trying though. They had pretty-much succeeding at creating synthetic ribosomes last time I looked.

Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA 3rd, Smith HO, & Venter JC (2010). Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome. Science (New York, N.Y.) PMID: 20488990

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Captain Skellett said...

I think the chances of making a really dangerous virus/bacteria using a synthetic genome is pretty low. If you mess around with genomes a lot they tend to die or not reproduce.

They might stick around in the lab, but if you tried to unleash it on the world I think they would be whipped into extinction pretty quick. imho. If I'm wrong, call me during the apocalypse.

Steven Salzberg said...

Hey Lab Rat,
I just noticed that you wrote about this. I think the press seriously over-hyped it, thanks no doubt to Venter's very active publicity operation. The NY Times got it right, though - there, Nicholas Wade pointed out that almost the same result was published by Venter's group 3 years ago, in 2007, when they transplanted one Mycoplasma genome into another, thus converting one species into another.

All the steps were very similar this time, with the one big difference being that the transplanted genome was synthesized this time, rather than extracted from another bacterium.

The NYT was also the only paper to point out that synthesizing a self-replicating organism from scratch had been done even earlier, by a different group from SUNY Stony Brook. In 2002, that group synthesized the polio virus de novo, and created functional viruses.

So the comment above - that the chances of making a "dangerous virus/bacteria using a synthetic genome is pretty low" - is incorrect. In fact, it has already been done.

Lab Rat said...

@Steven Salzberg: Thanks for the input. I was aware of the virus work done, but it must have slipped my memory while writing this up! It does seem to have been quite over-hyped, probably because the creation of new life makes a better and more headline-grabbing story than synthesising genomes and moving them around.

lifeandtechie said...

Hi Lab Rat,
Nice post that tracks closely with the way I've been thinking about this paper too. My two cents on this are here:

Anonymous said...


I've bet you've come across his future directions with this research; going into vaccine production for the common flu for example.

I think this advancement in creating synthetic genome is really just a tiny step towards limitless possibilities. If this was to advance out even further, really useful and beneficial things could really come out from this.

It seems really small that "hey, they're just trying to tweak a working genome and putting it in a working system" but it's really much more complex when you look at how much they've really gotten to understand how difficult it is in the first place. so yea. it's really just a small step that might explode to limitless wonders.

Lab Rat said...

@anonymous: I heard about the work done on the flu vaccine and found it really impressive - far more impressive than the synthetic genome as it was smaller scale work but with a huge number of potential applications (I'd like to blog about it but I can't find the paper).

There are a *huge* number of possibilities involved in synthetic biology, I agree, an it is a lovely field to be following and finding out about :)