Typical. One of the most anticipated technological breakthroughs in years hits the streets, and I’m completely off the web – holed up in an Italian hotel with no internet and no phone.
I’m talking of course about J. Craig Venter’s team’s breakthrough in synthesizing a living organism, almost from scratch – published in the journal Science on Thursday and speculated on by everyone from Nobel laureates to Vatican officials since…
Having followed synthetic biology for some time, I’ve been eagerly awaiting the announcement that Venter has finally created a synthetic organism. So I was more than a little frustrated to miss the first wave of commentaries on this week’s paper. And coming late to the game, I now find that “Venter Fatigue” is already setting in – making writing a blog that someone wants to read all the harder.
But there are issues and ideas that I think are still worth exploring here. So this is what I’m going to do:
For today, I thought I would recycle some stuff I wrote on what might be called “digital biology” last year – the potentially disruptive concept underlying synthetic biology that could well herald a new era of how we control the world we live in. Then, when I’ve had a bit more time to marshal my thoughts, I’ll aim to write something about risks and ethics – and especially the need to place discussions on a science basis, and not get over-distracted by ethical hand-wringing.
But back to “digital biology.” Last June, I wrote a piece about how our increasing control over matter at the nanoscale is transforming our ability to bend the world to our own ends. This is what I said about advances in manipulating DNA:
“Thirty years ago, the notion of controlling the code of life itself would have been laughable. Now it seems within reach.
Over the past few years, the ease with which genetic code can be sequenced has plummeted. It took 13 years for teams of scientists around the globe to first read the human genome – completing the project in 2001. In 2007, it took 2 months to sequence the genome of DNA-co-discoverer James Watson. And by 2013 it is likely that your personal genome could be read in the time it takes to boil an egg.
Of course, sequencing just reads the information – it doesn’t tell you how to use it. But here’s the important thing – sequencing genomes transforms the information from the physical domain to the digital domain, where it can be experimented with and engineered in new ways. While restricted to the physical world, there were always going to be limitations to how effectively we manipulated and controlled genetic material. In the digital domain, those limitations are gone. Cheap affordable sequencing is ushering in the age of digital biology.
However, playing around with genetic information on computers would be little more than a novelty if it weren’t for one further advance – the plummeting cost of DNA synthesis. This completes the loop between the physical and digital worlds. Now, once you have uploaded your genome into the computer and digitally enhanced it, the technology exists – or soon will – to download the new genome back into reality. It’s a technology that promises to enable an incredibly sophisticated level of genetic engineering. It allows brand new genetic code to be written on the computer, tested out in virtual space, then downloaded back into an organism. It even allows brand new organisms to be designed and created from scratch.
Synthetic biology - blurring the boundaries between the digital and physical domains
This possibility was pushed home last year when Craig Venter’s team synthesized the genome of a bacterium – Mycobacterium genitalium – from scratch. The team has yet to insert the synthesized DNA into a cell, and thus achieve – in effect – the creation of life from laboratory chemicals. But it seems only a matter of time before this is achieved.
We’re not quite there yet with the technology that will allow us to manipulate biology at the nanoscale. But it’s coming. And when it does, the level of control we have had over matter for the past ten centuries will seem like child’s play.”
This last week’s announcement takes the idea of designing living systems in the digital domain – then reading them back into reality – to the next level. Okay so you can split hairs and say that Venter and his crew didn’t technically synthesize life – they needed a few existing components (the machinery of the cell) to start with. But it really is splitting hairs, because the synthetic genome included the code that allowed this machinery to be constructed from scratch in subsequent generations of the organism. The breakthrough here was the ability to write the complete code for an organism on a computer, then translate it into a real, living, replicating life form.
Of course, there’s a ton of science that we don’t understand here – and given the enormous complexity of living organisms, it will be a long time before we come close to coming close to being able to design a completely new organism from scratch that does what we intend it to do. But that’s not the point here. What we are seeing is the beginning of a new technology, where what we understand is secondary to what we can do.
We may be a long way from perfectly designed organisms. But technology isn’t about perfection – it’s about doing something practical to achieve a tangible result. And to do that, you don’t always need to know why things work; just that they do work.
Without a doubt, this week’s announcement marks the dawn of a new technology – a technology that blurs the boundaries between the digital domain and living organisms. The state of the science may still be lacking. But then how often has a new technology been preceded by a mature science? Usually the technology and the science progress in tandem, and it’s not unusual for the technology to lead the science.
Add to this the incredible progress that has been made in engineering complex systems over the past 100 years – leading to technologies where the whole is greater than the contribution of any individual or team working on it – and the stage is set for Venter’s team’s achievements to profoundly influence how we interact with the living world.
The question is, are we up to handling it?
Note: apologies for an appallingly cliched title, although I was surprised no-one else has used it yet. Guess that’s what jetlag and internet deprivation do for you!
Yes we are up to handle it.
Nanoscale Control: Leveraging biology.
What we need to do is very simple: Harness synthetic biology for the manipulation of inorganic (and organic) nano-structures. That domain (synthetic biology) is where we are going to get the ability to manipulate in all three dimensions at the nano-scale with the most flexibility.
Actually, research into using DNA as an engineered molecule for making complex structures at the nanoscale rather than as the core of a living organism is very exciting – it seems that this is an extremely versatile molecule, and the more we can control and manipulate it, the more doors to innovative new technologies are opened.
You are right in that, indeed we shall both agree that ample progress in DNA based “origami” manufacturing and synthetic biology will in combination provide even more flexibility then either alone. I would like to invite you to observe this picture from the JCVI,
http://www.google.com/hostednews/ap/slideshow/ALeqM5ha2hIikQvHx347p3JzHAAdXUIIjAD9FRB9480?index=0
Observe the very stark features and know that within that we may design. The membrane structure is vital as it allows expansion of reaction networks into 3D, allowing us to harness the diffusive properties of components inside cells. This is vital, for we must realize that the DNA origami generally needs a fuel of some type, it also needs the “matter” which it will manipulate and form into product. My point here is that diffusion is a very valuable engineering tool.
Perhaps synthetic life merely can be understood as a degree of sophistication in our control of molecular reaction pathways. Who knows, it’s going to take a lot of science now to understand what we can make with synthetic biology. Our measurement tools still are not yet good enough to get an efficient “science”. The Stealth Bio probe is a step in the right direction though.
“What we are seeing is the beginning of a new technology, where what we understand is secondary to what we can do.”
I see your point here and quite agree with you but the use of ‘where what we understand is secondary to what we can do’ in this sentence in your article is unnecessary. You go on to make the point that quite often technology precedes the science. That bit of phrase confuses the reader and distracts him from the main argument which is that it is the birth of a new technology.
A concerned reader,
Akshat
My apologies that this confused you. But my point was that technology doesn’t always depend on understanding how things work – in fact the history of technology innovation suggests that it frequently preceded scientific understanding.
Andrew,
Both you and I can recognize an appalling cliche when we see one, but I get to one-up you here. Back in 2008, I attended a provocative “discussion” titled “Synthetic Biology: Coming Up Fast!” at the Woodrow Wilson International Center for Scholars, where you were working at the time. As managing editor of the American Chemical Society’s weekly Chemical & Engineering News at the time, I occasionally wrote the editorials. And I wrote one about what I learned at this discussion. I won’t repeat my observations here (http://cenblog.org/2008/12/life-as-we-dont-know-it/), but I will admit that I too could not resist using the life-as-we-don’t-know-it-cliche, though in a slight variation of the one you went with (probably why your Internet search did not capture it). Cliche it is, but it is spot on too. Life as we know it is the one global experiment of life and evolution that we have. It is our one magnificent, unfathomably expansive, superlatively consequential, awe-inspiring, 4-billion-year data point. Starting another data point ourselves should make our eyes wide as saucers and our minds reel, as though we have seen for the first time a roiling ocean whose resources and perils remain unknown even though we already have taken the plunge. As you say, “The question is, are we up to handling it?”
Have anyone received this article as well: ?
http://www.nature.com/nature/journal/vaop/ncurrent/pdf/465422a.pdf
Hmm, I don’t think you were quite meaning this as I have interpreted it Andrew, but I have to disagree with your point on the ethical hand-wringing, I think we should be distracting ourselves quite a lot with Ethical Hand-Wringing while the scientists are getting on with creating their new organisms, especially considering ‘where what we understand is secondary to what we can do’, as you said.
I was at the RS meeting which was filmed on Newsnight last week, (my Mum and I spotted me fleetingly in the vid!) and this and other recent synbio conversations made me smile. It was just like being at a nano seminar!
We must learn the lessons of nano and, more particularly, undertake significant Ethical Hand-Wringing further in advance than we did with nano, which was pretty much already in the shops when we got on the case.
Here are quick observations on my deja vu moments and lessons from nano that may apply. This is not an exhaustive list, just my quick on the hoof thoughts in response to the limited information I have:
This is just an evolution of….. what’s all the fuss about?’‘But it’s just an extension of GM’, ‘it’s just an extension of systems biology’, ‘it’s not actually anything really different’. Hello?! Whether that is true or not from a scientific point of view, much like nano when you are close to it, that is not the point. As the The Economist points out in its editorial this week, ‘…whatever the rational pleadings of physics and chemistry, there exists a sense that biology is different, is more than just the sum of atoms moving about and reacting with one another, is somehow infused with a divine spark, a vital essence’.
That has always been the line from nano scientists too, perhaps with even more validity, but to the lay person, or the sceptic it looks very dismissive and very suspicious. So though it is perhaps reasonable from a scientific point of view, I would suggest that synthetic biologists kill that ‘line of defence’, it won’t work and it never worked for nano either. Instead of calming fears, in fact it often has the opposite effect of raising further suspicions in the non-expert.
The Definition Question: Aaaahhhhh, nnnnoooooo! Guess what, there is no definition, and I had a big deja vu moment here, the conversation was IDENTICAL to the many I have had about nano over the years. Standards makers, regulators, synbiologists, whoever – get this sorted. This has been a very divisive issue for nano, some say deliberately, so pleeeeese address this question as soon as possible. I may be wrong, but there doesn’t seem to be a concerted international effort on this at the moment, there needs to be, now. An idea – call up some of the nano people and find out how to do it as slowly and tortuously as possible and then do it differently!
Governance – there is work going on worldwide on this, though it appears in academia, rather than a concerted international effort, though I may be wrong. 5 Academies, sister/brother orgs toe the Royal Academies are meeting to discuss synbio and this will be top of the list. Obviously we need to do much better with this than we have on nano.
For example the Venter Institute/MIT/CSIS did a paper on Options for Governance, in the UK Imperial/LSE/BIOS have a Center for Synthetic Biology and Innovation group is doing some work sponsored by the Royal Society and others which looks interesting and there are other ethicists and such like doing their own work.
But the lesson for me from nano, which with the potential for serious ‘bioerrors and bioterrors’, is even more important for synbio, is to get an international effort underway, ASAP, coordinated by a group such as the UN or OECD. I have a vision for a World Economic Forum/World Social Forum joint effort. How unlikely is that, but perhaps worth a try?
‘The regulation is fit for purpose, we don’t need any more’. This may actually be the case in this instance, but the time spent arguing about definition with nano has slowed down the potential evaluation of the need for regulation, and, some argue, given us some regulation which is not really fit for purpose.
Get business and science working together from the start. In nano there were and still are parallel discussions going on. We really need to do things differently for synbio. It is at the application end where the HSE and social and ethical issues really hit, and business and science need to understand each other, need to participate in these debates. If the governance area gets round by the Science Academies alone, this is unlikely to happen. We need to find ways of making those connections early and making them stick.
Ethical Hand-Wringing and public engagement. I have been encouraged by the calls for ethical debate, public engagement and what I think of as Ethical Hand-Wringing! However, what we have at the moment are some useful and interesting sets of focus groups. This is not a debate on synthetic biology that reaches people and allows them to debate and influence policy and science. So what are we going to do about that?
Obviously synbioandme.org (yes I have bagged the domain!) would be a start! But I have come to the conclusion that we need to have mass communication and mass engagement. This is tricky, expensive and needs much more than a few focus groups to pull off. We need to be much more innovative this time round, and I don’t see much signs of that at the moment. Though of course as we are all broke, it won’t be happening anytime soon!
There time is now to do this. To really learn the lessons from GM and Nano and generate a real international effort on governance, standards and public engagement, we need to get going soon.
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