MainlyMartian

Synthetic Biology 2.0: Nature product

I meant to do a wrap-up post, but travel and poor connectivity intervened. Rob Carlson had a last post on the conference that I found intriguing, but  I will content myself by pointing to Erika Check's news report on the meeting in Nature, and an editorial that accompanied it. Here's the nub of the argument:

Self-governance need not and should not be exclusive — it does not preclude other forms of governance, any more than the possession of conscience makes redundant the strictures of law. It is hard not to suspect that the problem with self-governance from the point of view of the letter-writers is that it could go some way to addressing potential problems that would make good campaigning issues.

The ability of human societies to modify and transform biological systems will increase more in this century than it has in the hundred centuries since the dawn of agriculture, regardless of whether the transformation unfolds under the rubric of 'synthetic biology'. Or, at least, we must hope that it will — as the only credible alternative is a future in which massive social upheaval, armed conflict or natural disaster halts the progress of scientific knowledge. The challenge is to foster a matching, or at least sufficient, increase in the wisdom and accountability with which these abilities are used.

That challenge will require changes in the law and customs, in ideology and theology, and in education and economics. No scientific community can be expected to shoulder all that on its own, and nor should it. Scientists who are alive to the possibilities of change, anxious to keep their house in order and be seen to be doing so, and keen to discuss the issues with the world, are part of the solution, not part of the problem.

Update: I'm informed by the excellent Kevin Costa that the webcast of the SB2.0 talks is now archived for online viewing here, and will soon be added to Google Video for podcasting. The community declaration, which is still a work in progress as of June 13th,  can be viewed here.

Synthetic Biology 2.0: More bloggers

Crossposted from the Nature Newsblog; to comment, please use the version there.

Alex Mallet, from Drew Endy's lab, gives his take on the whole meeting here. And a student at Davidson college has lots of entries summarising specific talks on cis-action. In the long run, I expect the easiest way to browse them will be on the May archive.

Four active bloggers at a small biology meeting: the shape of things to come? or an outlier produced by an over-representation of geekiness in this very specific field?

Synthetic Biology 2.0: Medicine (and its malcontents?)

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.

Synthetic Biology 2.0: Also blogging the meeting...

...is Rob Carlson, a friend who I met at the first of these meetings. Rob, like Drew Endy, used to work at Roger Brent's Molecular Sciences Institute, just down the road from here, and he's now at the University of Washington. He may well be the only person in this pretty eclectic audience whose interests roam from detecting single proteins in cells to building space elevators. More on Rob here.

Rob's latest post from the meeting points out its commercial vibe. I must say that I wish I'd noticed Craig Venter and Vinod Khosla talking over lunch -- or indeed heard what they were saying... Rob also catches up with a couple of this morning's chemistry talks, so for the time being at least I won't.

Posting on Rob reminds of something I wrote about the biosecurity implications of synthetic biology in the New York Times last year. It seems particularly apposite right now, because the past two talks have been about designing bacteria and viruses for therapeutic purposes, part of which might involve making them less susceptible to the immune system. Subscribers can find it here, and everyone else can apparently find it for free here, but I should point out that the free version contains an error that crept into my copy through miscommunication with the Times, and which the Times itself has corrected: though Rob was a key player in the conception of very sensitive detection molecules called "tadpoles", there are a bunch of other people who should share credit, most specifically Ian Burbulis. The relevant paper is Burbulis, I.E., Yamaguchi, K., Carlson, R., and Brent, R. "Using protein-DNA chimera to count small numbers of molecules". Nature Methods Vol. 2, 31-37, 2005

Update: the shadow version of the Times story has been corrected to list all authors

Synthetic Biology 2.0: Opposing views

Tim Gardner, of Boston University, gave an interesting talk this morning on the "network biology" approaches he's using in his lab. Interesting in two distinct ways.

One: interesting in itself. Looking for networks by comparing the RNA expression of cells in different conditions and looking for correlations (or, more precisely, according to Gardner, "mutual information") between the expression of regulatory sequences and genes is a neat way of learning more about how cells actually work, a subject on which we are often remarkably ignorant. Key factoid (if I understood it correctly): in E. coli, the best studied bacterium, researchers currently don't have any idea of how three quarters of the genes are regulated. And that shouldn't be taken as meaning that we understand fully how the other quarter is regulated -- just that in those cases we have some leads on the subject (and, to be fair, in some of those cases much more than that).

Second interesting thing: Gardner's take-home message is the exact opposite of the view taken by Drew Endy and his colleagues. Gardner argues that because we have very few well characterised "components" with which to build entirely novel mechanisms and don't really understand how to do so we should concentrate on learning how natural cells work through building network models and get our miracles by tweaking these natural systems. Endy's position is that working out how natural systems actually work is extraordinarily hard (remember that ignorance over three quarters of E. coli) and that we should instead try and build simple things which we do understand. In this respect synthetic biology exists as a counterpoint, or alternative, to systems biology, network biology and other attempts to uncover the ways life actually works.

In part, this is the division between science and engineering. Endy and many of his colleagues at MIT are engineers, and they think in terms of designing well characterised systems, not of understanding very poorly characterised systems such as those that four billion years of evolution have left littering the face of the earth. As Endy puts it, if you were faced with a very complex, very buggy, awesomely antique software system which had been re-worked billions of times, with no notes at all to reveal what all that rewriting was meant to accomplish, or any really well understood sense of what its operating principles were, wouldn't you rather design something new from scratch?

The idea that synthetic biology offers that ability to do wholly new things is often seen as underwriting its practical or commercial possibilities. But it is also, at a more fundamental level, an epistemological distinction that sets this new discipline apart from its predecessors, offering real intellectual novelty. If, that is, Endy and his engineering colleagues can really deliver. Otherwise, it's biology as usual -- even if that biology is, as Garnder's talk was, very interesting in its own right.

I'll try and get a sense of which side of this debate the people attending the conference can be found on; if I turn up anything, I'll report back.

Update: I originally characterised the "mutual information" approach as a way of looking at things "more loosely but more productively", but Rob put me right.

This has now been crossposted onto the Nature Newsblog. If moved to comment, please do so there.

Synthetic Biology 2.0: Fun to come

An interesting addition to the various agendas surrounding this conference is an open letter from a variety of NGOs concerned about the implications of the technology and the limitations of scientific self governance, which can be read here. I hope some of those involved will be able to present their position in person during the debates on these issues that will take place on the third day of the conference -- I understand there are currently some invitations in the ether.

As I mentioned in a previous post, I'm chairing a session on that third day, which puts me in a position which might be seen as leading to a conflict of interest. For what it's worth, I do think there are issues with journalists reporting on conferences at which they are also participating, but I don't think those issues mean that such reporting is always a no-no, provided that the appropriate disclaimers are in place. But it does mean that I don't think I'm going to express my opinions on these particular issues right now.

This has now been crossposted onto the Nature Newsblog. If moved to comment, please do so there.

Synthetic Biology 2.0: BTUs per bushel

A fascinating first presentation from Steve Chu, who runs Lawrence Berkeley Lab, one of the sponsors of this event, on the challenge of finding technologies for clean energy production and the possibilities that various synthetic-biology technologies offer for meeting that challenge. There was lots of talk of artificial photosynthesis, and some wonderfully far out ideas, such as redesigning plants so that their carbon-dioxide intakes and water outputs are separated, rather than being combined in the magnificently subtle mechanisms of the stomata. I suspect that this is not in fact practical or desirable, but maybe I've been hanging out too long with the plant scientists who Chu has found critical of this idea. Chu, in response, says the plant people might benefit from learning to think like physicists or science fiction authors, and I'm not one to play down the possibilities of learning from SF. What's more, the fact that the set of "things which are subtler than physicists think" is pretty much equal to the observable universe doesn't mean that physicists don't have wonderful insights to offer to everyone else, even if the tone in which those insights are offered can, occasionally, be a little hard to take. Anyway, even if the disambiguated stomata never come to pass, or don't deliver advantages, they still represent an idea about photosynthesis that I, as someone with a book on the subject inching towards publication, have never come across before, so lots of extra credit for freshness.

Much more practical is the two-pronged strategy Chu outlined for improving biomass systems: re-engineer the plants to be more easily converted into fuel (eg less lignin), and re-engineer various microbes to be better at carrying out that conversion directly. It makes a lot of sense, though there are some fairly subtle questions of sustainability that need to be addressed, at least as far as I'm concerned, before we can safely assume that large-scale agricultural systems will provide a significant fraction of our future fuel needs.

What didn't make a lot of sense, to European ears, was the way in which some of this was expressed. "Gallons per acre"? Please! They'll be talking about BTUs per bushel next. 21st century science and technology really shouldn't be expressed in sixteenth century units.

This has now been crossposted onto the Nature Newsblog. If moved to comment, please do so there.

Synthetic Biology 2.0: What's afoot?

This post and those which follow should really be going up on the Nature Newsblog (part of my day-job duties as the chief news and features editor of that great journal), but due to a fairly predictable snafu which is mostly my fault I don't seem to be able to post there at the moment, so I'm putting it up here and will probably get it cross posted there in due course. Alert readers will notice that what follows is not very martian, and those whose interest in planets doesn't extend to attempts to rewire the life forms of this one are advised to skip it.

It's always fun to come to a conference where something is afoot -- where there's not just a bunch of presentations, but a genuine agenda. The first synthetic biology conference, at MIT two years ago, was such a conference -- an attempt to bring together a whole bunch of people working on a diverse bunch of technologies and scientific approaches that are made possible by cheap DNA synthesis, and to some extent to establish the pre-eminence among those approaches of the vision of synthetic biology then being championed at MIT. That vision is of a world where biological circuits can be designed from scratch, using "biobricks", in an analgous way to electronic circuits, but with standardised sequences of DNA and the proteins they describe taking the place of resistors, transistors, diodes and the like. The conference was the basis of a feature I wrote on synthetic biology for Wired in my previous existence.

Two years on, here we all are at Synthetic Biology 2.0, the followup conference, at UC Berkley. And again its a conference with an agenda. Or, more properly, many agendas. The main one, I think, is to reassert the message of Synthetic Biology 1.0 -- that lots of different things people are doing with different biological systems can be treated as a coherent emerging discipline. But there are also a bunch of other things going on, among them: an attempt to show that this sort of stuff has real world applications, especially in the energy arena; a showcase for the fact that this technology has commercial possibilities (various companies have sprung up in the field in the past two years, including Craig Venter's Synthetic Genomics and Codon Devices, which boasts on its board Drew Endy, the most eloquent of the proponents of the "MIT vision" described above; an attempt to get the nasc ent community to agree how to regulate itself and to avoid this technology being used for naughty purposes; a window to show the world that this technology, well regulated, can be a force for good.

Not all these agendas are necessarily aligned. For example, without being unduly cynical, there could be commercial applications, at least in the short term, even if there aren't dramatic real world applications. And self regulation could easily co-exist with, or indeed reinforce, public worries. And not everyone here will sign up to all or indeed any of them. So it will be interesting to see how it all unfolds, especially on the third day, where the science and society implications are going to be discussed. (Disclaimer: I will be moderating one of the sessions on that day.)

This has now been crossposted onto the Nature Newsblog. If moved to comment, please do so there.