Life less ordinary

It is tempting to take predictions of a ‘new industrial revolution’ with a very large pinch of salt. But when these words are said by the senior dean of the Faculty of Engineering at Imperial College, and have the backing of some of the sharpest scientific minds in the business, it’s perhaps time to sit up, listen, and put the knee-jerk scepticism on hold.

Prof Richard Kitney is heading the college’s newly-launched Institute of Systems Biology, a body that brings together engineers, mathematicians and physical scientists in an effort to address some of the world’s most pressing medical and biological challenges.

Kitney believes that by applying engineering techniques and technologies to biological problems, the institute could, among other things, take important steps towards a cure for cancer, advance our understanding of diseases from the sub-cellular right up to the population level, and pave the way for the development of the world’s first biological computer. He is also convinced that, with political backing, the UK has the foundations in place to become a world leader in this emerging field.

While the sub-cellular biological world might sound a million miles away from the factory floor, core engineering skills will be contributing to the institute’s work through three main technology areas: imaging and visualisation; mathematical modelling; and the development of hardware, such as new types of sensor.

Much of the group’s work on imaging will be concerned with developing new signal and image processing techniques to improve existing medical systems such as Magnetic Resonance (MR) and Positron Emission Tomography (PET) scanning. It is also working on the further development of new types of scanning techniques that operate at the cellular and sub-cellular level such as atomic force microscopy.

The kind of mathematical modelling tools familiar in other areas of engineering will also play a key role in the group’s research, explained Kitney. ‘If you think of the engineering cycle — in the development of an aircraft engine, for instance — you start off with a specification. on this basis you produce a design, followed by a lot of modelling, then the realisation and testing of the device. Once you’ve carried out the testing you go back and look at the specification again.

‘That is exactly the technique we’re applying here within the institute to many biological problems — such as analysing the way that protein is synthesised, and then looking at its specification, the way it works and applying a great deal of modelling.’

Kitney explained that a number of modelling approaches are being taken straight from engineering and applied to biology. ‘for instance, you can now apply the same type of modelling techniques you apply to cellular networks for mobile phones to the area of looking at cells and the complexity of the communication,’ he said.

The group is also looking into the physiological applications of the kind of multiple feedback loop techniques typically used to design and test things such as aircraft systems. One area where this approach is proving useful, explained Kitney, is in the analysis of blood pressure control systems.

‘If you’re asleep for eight hours and suddenly jump up, you’re going from horizontal to vertical so your blood pressure immediately drops — but there’s a very sophisticated control system in your body that immediately compensates for that. There are multiple control loops. The first thing that kicks in is an increase in heart rate, replaced over a period of 30 seconds by a change in the diameters of the blood vessels to push up the blood pressure.

‘On a longer term basis you can increase the amount of blood that comes out of the heart. There are three control loops. In the same way as you have multiple control loops in an aircraft and model those, that’s exactly what we do here, and we model it using non-linear control theory — which comes directly out of engineering.’

Alongside such techniques, the institute is also engaged in the development of engineering hardware, and in particular new types of sensor. Non-destructive testing is one area of particular interest. Kitney explained that the kind of ultrasonic probes used to look for cracks in aircraft engines are now being re-applied as micro-transducers that can be deployed inside arteries to look for the tell-tale signs of arterial disease.

One of the most striking ways in which this range of systems biology techniques will benefit humanity, said Kitney, is that they will enable researchers within the medical faculty to turn their attention to molecular-based medicine, and analyse in detail why some people are genetically prone to certain types of disease.

He held up cystic fibrosis as an area where this approach is already paying dividends. ‘biologists managed to identify the gene that causes this and are now working towards its modification. Potentially you have the situation where if a baby is identified as being a candidate for cystic fibrosis you can modify that gene. In a much more systematic way, systems biology will enable us to replicate that approach across a whole series of diseases. I’m sure that over the next 20 years there will be massive inroads into the basis of many cancers.’

Perhaps even more intriguingly, the institute is also investigating the area of synthetic biology where an engineering science approach is taken to the development of new types of biologically-based devices. Kitney explained that by, for instance, modifying strips of bacterial DNA, it will actually be possible to produce standard ‘parts’ with well-defined characteristics.

The current state of the technology is, he said, reminiscent of the early days of the electronics industry. ‘If you go back 50 years to when the first diodes and transistors were being produced, there were high levels of noise and a lot of variability. Engineers squeezed out the noise, and made the characteristics of these devices accurate so they became standardised. That’s exactly what we’re attempting to do here — take strips of DNA, define their characteristics and get those levels of noise down.’

One of the really long-term goals of this initiative is to develop so-called biological computers — tiny biologically-based electronic devices that could be replicated throughout all of the cells of the body.

It may sound like the stuff of science fiction, but Kitney said that the basic building blocks for a biological computer have already been developed. ‘For a computer, broadly speaking you need two things — a clock and an AND gate. Within my joint research group we’ve already produced a biologically-based oscillator, which is effectively a clock, and ETH Zurich have actually produced AND gates.’

Kitney said that while such devices are incredibly slow when compared to conventional computers — switching over hours rather the nanoseconds — they could have mind-boggling applications. ‘If you want to introduce a computer into a cell you cannot do it with standard electronic devices. If you can do it with a biologically-based device small enough to derive its power from the surrounding environment then you start to have computing applications that could be incredibly valuable. It could be used to monitor changes in cell structure or mutation leading to cancer.’

Although these developments are at least 30 years away, Kitney is confident that he and his colleagues don’t have their heads in the clouds. ‘Many people think this is crazy. all I can say is that I and a number of my colleagues at MIT and Imperial really believe in this stuff. We could all be wrong but when you look at the pedigree of these people they have a really good track record of spotting winners.’

Kitney passionately believes that synthetic biology is going to be incredibly important for the future of engineering, and that the UK is extremely well placed in terms of the basic research.

But he warned that scientists and politicians must talk to each other if the UK’s mistakes of the past are not to be revisited. ‘Back in the 1970s, this country, in my view, completely missed out on the microchip revolution which has driven the world economy for the past 10-15 years because we couldn’t get the decision-makers to understand its importance.’

Will the UK lose out again, and can it build on its expertise? ‘It’s always difficult — I know it’s a cliché, but it’s also true: we produce fantastic R&D but then commercialisation is often done by others. With the major industrial developments occurring in china and India, for example, the only thing that will keep western Europe going is its brainpower — that’s why there has to be a continuum from the research universities through into industry.

‘I think we’re on the cusp of a third industrial revolution — one that is biologically based. It’s going to be massive.’