Will nanotechnology lead to a truly synthetic biology?

This piece was written in response to an invitation from the management consultants McKinsey to contribute to a forthcoming publication discussing the potential impacts of biotechnology in the coming century. This is the unedited version, which is quite a lot longer than the version that will be published.

The discovery of an alien form of life would be discovery of the century, with profound scientific and philosophical implications. Within the next fifty years, there’s a serious chance that we’ll make this discovery, not by finding life on a distant planet or indeed by such aliens visiting us on earth, but by creating this new form of life ourselves. This will be the logical conclusion of using the developing tools of nanotechnology to develop a “bottom-up” version of synthetic biology, which instead of rearranging and redesigning the existing components of “normal” biology, as currently popular visions of synthetic biology propose, uses the inspiration of biology to synthesise entirely novel systems.

Life on earth is characterised by a stupendous variety of external forms and ways of life. To us, it’s the differences between mammals like us and insects, trees and fungi that seem most obvious, while there’s a vast variety of other unfamiliar and invisible organisms that are outside our everyday experience. Yet, underneath all this variety there’s a common set of components that underlies all biology. There’s a common genetic code, based on the molecule DNA, and in the nanoscale machinery that underlies the operation of life, based on proteins, there are remarkable continuities between organisms that on the surface seem utterly different. That all life is based on the same type of molecular biology – with information stored in DNA, transcribed through RNA to be materialised in the form of machines and enzymes made out of proteins – reflects the fact that all the life we know about has evolved from a common ancestor. Alien life is a staple of science fiction, of course, and people have speculated for many years that if life evolved elsewhere it might well be based on an entirely different set of basic components. Do developments of nanotechnology and synthetic biology mean that we can go beyond speculation to experiment?

Certainly, the emerging discipline of synthetic biology is currently attracting excitement and foreboding in equal measure. It’s important to realise, though, that in the most extensively promoted visions of synthetic biology now, what’s proposed isn’t making entirely new kinds of life. Rather than aiming to make a new type of wholly synthetic alien life, what is proposed is to radically re-engineer existing life forms. In one vision, it is proposed to identify in living systems independent parts or modules, that could be reassembled to achieve new, radically modified organisms that can deliver some desired outcome, for example synthesising a particularly complicated molecule. In one important example of this approach, researchers at Lawrence Berkeley National Laboratory developed a strain of E. coli that synthesises a precursor to artmesinin, a potent (and expensive) anti-malarial drug. In a sense, this field is a reaction to the discovery that genetic modification of organisms is more difficult than previously thought; rather than being able to get what one wants from an organism by altering a single gene, one often needs to re-engineer entire regulatory and signalling pathways. In these complex processes, protein molecules – enzymes – essentially function as molecular switches, which respond to the presence of other molecules by initiating further chemical changes. It’s become commonplace to make analogies between these complex chemical networks and electronic circuits, and in this analogy this kind of synthetic biology can be thought of as the wholesale rewiring of the (biochemical) circuits which control the operation of an organism. The well-publicised proposals of Craig Venter are even more radical – their project is to create a single-celled organism that has been slimmed down to have only the minimal functions consistent with life, and then to replace its genetic material with a new, entirely artificial, genome created in the lab from synthetic DNA. The analogy used here is that one is “rebooting” the cell with a new “operating system”. Dramatic as this proposal sounds, though, the artificial life-form that would be created would still be based on the same biochemical components as natural life. It might be synthetic life, but it’s not alien.

So what would it take to make a synthetic life-form that was truly alien? In principle, it seems difficult to argue that this wouldn’t be possible in principle – as we learn more about the details of the way cell biology works, we can see that it is intricate and marvellous, but in no sense miraculous – it’s based on machinery that operates on principles consistent with the way we know physical laws operate on the nano-scale. These principles, it should be said, are very different to the ones that underlie the sorts of engineering we are used to on the macro-scale; nanotechnologists have a huge amount to learn from biology. But we are already seeing very crude examples of synthetic nanostructures and devices that use some of the design principles of biology – designed molecules that self-assemble to make molecular bags that resemble cell membranes; pores that open and close to let molecules in and out of these enclosures, molecules that recognise other molecules and respond by changes in shape. It’s quite conceivable to imagine these components being improved and integrated into systems. One could imagine a proto-cell, with pores controlling traffic of molecules in and out of it, containing an network of molecules and machines that together added up to a metabolism, taking in energy and chemicals from the environment and using them to make the components needed for the system to maintain itself, grow and perhaps reproduce.

Would such a proto-cell truly constitute an artificial alien-life form? The answer to this question, of course, depends on how we define life. But experimental progress in this direction will itself help answer this thorny question, or at least allow us to pose it more precisely. The fundamental problem we have when trying to talk about the properties of life in general, is that we only know about a single example. Only when we have some examples of alien life will it be possible to talk about the general laws, not of biology, but of all possible biologies. The quest to make artificial alien life will teach us much about the origins of our kind of life. Experimental research into the origins of life consists of an attempt to rerun the origins of our kind of life in the early history of earth, and is in effect an attempt to create artificial alien life from those molecules that can plausibly be argued to have been present on the early earth. Using nanotechnology to make a functioning proto-cell should be an easier task than this, as we don’t have to restrict ourselves to the kinds of materials that were naturally occurring on the early earth.

Creating artificial alien life would be a breathtaking piece of science, but it’s natural to ask whether it would have any practical use. The selling point of the most currently popular visions of synthetic biology is that they will permit us to do difficult chemical transformations in much more effective ways – making hydrogen from sunlight and water, for example, or making complex molecules for pharmaceutical uses. Conventional life, including the modifications proposed by synthetic biology, operates only in a restricted range of environments, so it’s possible to imagine that one could make a type of alien life that operated in quite different environments – at high temperatures, in liquid metals, for example – opening up entirely different types of chemistry. These utilitarian considerations, though, pale in comparison to what would be implied more broadly if we made a technology that had a life of its own.

A synthetic, DNA based molecular motor

The molecule DNA has emerged as the building block of choice for making precise, self-assembled nanoscale structures (in the laboratory, at least) – the specificity of the base-pair interaction makes it possible to design DNA sequences which will spontaneously form rather intricate structures. The field was founded by NYU’s Nadrian Seeman; I’ve written here before about DNA nanostructures from Erik Winfree and Paul Rothemund at Caltech, and Andrew Turberfield at Oxford. Now from Turberfield’s group comes a paper showing that DNA has the potential not just to make static structures, but to make functioning machines.

The paper, Coordinated Chemomechanical Cycles: A Mechanism for Autonomous Molecular Motion (abstract, subscription required for full article), by Simon Green, Jonathan Bath and Andrew Turberfield , was published in Physical Review Letters a couple of weeks ago (see also this Physical Review Focus article). The aim of the research was to design a synthetic analogue of the molecular motors that are so important in biology – these convert chemical energy (in biology, typically from a fuel like the energy carrying molecule ATP) into mechanical energy. One important class of biological motors consists of something like a molecular walker which moves along a track – for example, the motor molecule myosin walks along an actin track to make our muscles contract, while kinesin walks along the microtubule network inside a cell to deliver molecules to where they are needed (to see how this works take a look at this video from Ron Vale at UCSF). What Turberfield’s group has demonstrated is a synthetic DNA based motor that walks along a DNA track when fed with a chemical fuel.

The way molecular motors work is very different to any motor we know about in our macroscopic world. They’re the archetypal “soft machines”, whose operation depends on the constant Brownian motion of the wet nanoscale world. The animation below shows a schematic of the motor cycle of the DNA motor. At rest, the motor is stuck down by both feet onto the track, which is also made of DNA. The first step is that a fuel molecule displaces one foot from the track; the foot part of the motor then catalyses the combination of this fuel molecule with another fuel molecule from the solution, releasing some chemical energy in the process. The foot is then free to bind back to the track again. The key point is that all these binding and unbinding events, together with the flexing of the components of the motor that allow it to pick up and put down its feet on the track are driven by the random buffetings of Brownian motion. What makes it work as a motor is the fact that there’s an asymmetry to which foot is more likely to be displaced from the track; when the foot sticks back each of the two possible positions is equally probable. This means that although each step in the motor is probabalistic, not deterministic, there’s a net movement, on average, in one direction. It’s the input of chemical energy of the fuel that breaks the symmetry between forward and backward motion, making this motor a physical realisation of a “Brownian ratchet”.

In this paper the authors don’t directly show the motor in action – rather, they demonstrate experimentally the presence of the various bound and unbound states. But this does allow them to make a good estimate of the forces that the motor can be expected to exert – a few picoNewtons, very much in the ball-park of the forces exerted by biological motors.

Schematic showing the operation of the DNA motor. Animation by Jonathan Bath.

Top US energy role for leading nanoscientist

It’s being reported that US President-Elect Obama will name the physicist Steven Chu as his Energy Secretary. Chu won the Nobel prize in 1997 (with Bill Phillips and Claude Cohen-Tannoudji) for his work on cooling and trapping atoms with laser light. One of the spin-offs from his discovery was the development of the “optical tweezers” technique, by which micron-size particles can be held and manipulated by a highly focused laser beam. Chu himself used this technique to manipulate individual DNA molecules, directly verifying the reptation theory of motion of long, entangled molecules. The technique has since become one of the mainstays of single molecule biophysics, used by a number of groups to characterise the properties of biological molecular motors.

Chu is currently director of the Lawrence Berkeley National Laboratory, where one of his major initiatives has been to launch a major initiative to develop economic methods for harnessing solar energy on a large scale – Helios. One can get some idea of what Chu’s priorities are from looking at recent talks he has given, for example this one: The energy problem and how we might solve it (PDF). This concludes with these words: ‘“We believe that aggressive support of energy science and technology, coupled with incentives that accelerate the concurrent development and deployment of innovative solutions, can transform the entire landscape of energy demand and supply … What the world does in the coming decade will have enormous consequences that will last for centuries; it is imperative that we begin without further delay.”

Overcoming nanophobia-phobia

It’s all too easy to worry about what the public thinks of nanotechnology, while forgetting that the public isn’t at all homogenous, and that their attitude will depend on their existing values and preconceptions. Three papers in the current issue of Nature Nanotechnology explore this issue. Dan Kahan and coworkers test the idea that, if people learn more about nanotechnology, they will tend to become more positive about it. Not so, they say: while people who support free markets and respect the authority of hierarchies find more to like in nanotechnology the more they learn, people with more egalitarian and communitarian views find more to worry about. Nick Pidgeon and his coworkers look for national differences, conducting parallel public engagement exercises in the UK and the USA. They find a somewhat surprising uniformity in views across the Atlantic, with both sets of people optimistic about potential benefits, particularly in the energy area. There are some national differences, with a greater consciousness of the possibility of regulatory failure in the UK (connected to recent history of the GMO debate and the BSE crisis), and a more consumerist attitude to potential medical benefits in the USA. The biggest media interest (see, for example, this BBC piece) has been attracted by Dietram Scheufele’s team’s suggestion that a dismissal of nanotechnology as morally unacceptable is correlated with religiosity, and that as a consequence nanotechnology is more publicly acceptable in the relatively irreligious countries of Europe than in the USA (see also Scheufele’s own blog).

I’ve written at greater length about these findings in this opinion piece on the Nature News website. I think many scientists will agree with Tim Harper that it’s a category error to ask whether “nanotechnology” is morally acceptable or unacceptable. A related question that occurs to me is this: when we compare public responses in the USA and Europe, how much of the difference is due to the religiosity of the members of the public being asked, and how much is due to the way nanotechnology is popularly framed on either side of the Atlantic? It’s notable that Scheufele’s paper illustrates the potential conflict between religion and nanotechnology (and converging technologies more generally) with a couple of papers about human enhancement, and a commentary by a Lutheran on the full Drexlerian vision of nanotechnology, all of which come from the USA. My sense is that this explicit connection of nanotechnology to human enhancement and transhumanism is much less prominent in Europe than the USA. Maybe it’s not so much the religiosity of the public that’s important in determining people’s attitudes, but the fervour of the people who are promoting nanotechnology.

Talking nanotechnology on the street

The BBC’s Radio 4 has been running a series of short programs – Street Science – featuring scientists being sent out onto the streets to engage random members of the public about controversial bits of science. The latest program dealt with nanotechnology, with my friend and colleague Tony Ryan getting a good hearing in the centre of Sheffield. The programme (RealPlayer file) is well worth a listen, as he talks about applications in medicine and novel photovoltaics, how 2-in-1 shampoo works, Fantastic Voyage, Prince Charles and grey goo, the potential dangers of carbon nanotubes, and why nanosilver-based odour resistant socks may not be a good idea.


Eric Drexler, the author of Nanosystems and Engines of Creation, launches his own blog today – Metamodern. The topics he’s covered so far include DNA nanotechnology and nanoplasmonics; these, to my mind, are a couple of the most exciting areas of modern nanoscience.

In the various debates about nanotechnology that have taken place over the years, not least on this blog, one sometimes has the sense that some of the people who presume to speak on behalf of Drexler and his ideas aren’t necessarily doing him any favours, so I’m looking forward to reading about what Drexler is thinking about now, directly from the source.