A big difference between this meeting and the one two years ago is the stress on medicine, which has been taking up quite a lot of Sunday. Wendell Lim, of UCSF, chairing the session, started it off with a serious, provocative vision. The medical implications of synthetic chemistry have been in making small molecule therapies; the medical implications of synthetic biology will lie in making "living therapies". Living therapies are creatures designed, with the help of synthetic genomes or parts of genomes, to do medicinal stuff. Examples from today: therapeutic bacteria that target tumours (bacteria seem attracted to tumours, which I didn't know before, and I'd be interested in finding out if anyone knows why), viruses for delivering genes, engineered immune system cells.
The immune cells came from David Baltimore, speaking this afternoon, who talked about various aspects of his project to "engineer immunity". The logic here is that it is difficult to develop vaccines against diseases such as AIDS and malaria because the immune system just isn't very good at dealing with them; if it were, the diseases wouldn't be such a problem. The fact that the natural immune response is so poor makes it hard to provoke a good response using vaccines. Wouldn't it be nice, goes Baltimore's argument, if we could get round this by going in and telling the immune system exactly what it should be doing, rather than just giving it a sketch of the problem -- that is, a vaccine -- and leaving it to its own insufficient devices. So, for example, give it blueprints of specific antibodies that are known to have a neutralising effect on HIV, rather than make do with the less impressive specimens it comes up with on its own. Or give it some stem cells that will make T-cells that we know will deal with a specific tumour.
Baltimore admits that this is ambitious stuff; it effectively combines immunotherapy, stem cell therapy and gene therapy, none of which, to put it kindly, are exactly established successes. But there are some encouraging results, and the potential pay offs are obviously vast.
Two thoughts here: one is that Baltimore's project, which has attracted the attention of the Bill and Melinda Gates Foundation, might be seen to some extent as old wine in new bottles -- ideas that have been around for a while and perhaps lsot some lustre rebadged in shiny up-to-date livery. Gene therapy has, after all, been in trials since 1990. In fact, though, I think re-examining the idea as synthetic biology makes sense. Synthetic biology is largely about reprogramming biological systems, and that's what gene therapy tries to do. If including gene therapy makes you reexamine what you think synthetic biology is, then maybe it should -- maybe synthetic biology is a bigger, broader thing than people are mostly taking it for.
Second thought: as these technologies get nearer to medicine, they also get scarier. Making viruses less likely to be recognised by a pre-existing immune response is a good idea for gene therapy, but it obviously has other potential implications. Likewise getting bacteria to last longer in the bloodstream and to express new proteins, such as invasin, that get them into cells, as described in one of the talks, is something that might be quite unpleasant in the wrong hands. So might associated systems that trigger pathogenic behaviour with an external cue. Imagine a harmless bacteria that could be spread through a population unobserved and then be triggered to turn nasty by a gas -- a gas that was not in itself a weapon, and so not recognised as such. That would be seriously nasty stuff.
The people doing this work are devoted to trying to do good. But systems for getting "living therapies" into the body to do good are obviously going to have overlaps with techniques for getting living weapons in to do harm. As I argued last year, biology has a dark side. This is not a reason for not doing such research -- but it is a reason for staying careful and thoughtful while doing so. This is something that the meeting will be returning to tomorrow.
(There are other worries, too. As Baltimore pointed out when he was talking about his expectation that lentiviruses would not have the leukaemia-causing problem that has dogged some gene therapy, it seems possible that the gene which was used in those trials was itself an oncogene. As Baltimore said, this was unfortunate. Also a little sobering.)
This has now been crossposted onto the Nature Newsblog. If moved to comment, please do so there.
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