Earlier this month, the UK’s Royal Academy of Engineering and Academy of Medical Sciences released a joint report that recommends the investment of £325 million ($640 million) over 10 years to establish three to five new systems biology centers at leading UK universities.
The report, Systems Biology: a Vision for Engineering and Medicine, is the outcome of a 13-member working group comprised of representatives of the two academies.
BioInform recently spoke to Richard Kitney, professor of biomedical systems engineering at Imperial College, London, and co-chair of the working group, about the report’s recommendations.
Can you tell me a bit about the motivation behind this report?
There’s a bit of background there. Basically, in 2003, it was the 50th anniversary of the publication of Watson and Crick’s paper on the double helix, and there were a series of lectures here in the UK about this, and one of the lectures was put on by the Royal Academy of Engineering, and I was asked to give this lecture. During this lecture, I talked basically about the important developments that have occurred over the past 50 years in molecular biology and cell biology, and how that was paralleled by developments in engineering, in terms of computer software, et cetera. And basically out of that lecture, [I created] a written version of it, and that made me think a lot more about where this whole field was going. So about three yeas ago, it must have been early 2004, I became keen on the idea of systems biology having an impact on engineering, and also engineering having an impact of systems biology.
In May of 2004, there was an approach by the Academy of Medical Sciences with a view to look at common areas we could work on. I went to a meeting, and there were about six people including Sir Colin Dollery [senior consultant at GlaxoSmithKline and a fellow of the Academy of Medical Sciences], who ultimately co-chaired the systems biology inquiry. Now Sir Colin Dollery is a very well known pharmacologist, and when we were kicking around ideas at this meeting, we both said that we thought systems biology was incredibly important, but for different reasons actually.
What happened was that during the autumn of 2004, we both wrote position papers to our academies saying that we should have an inquiry into systems biology, and that’s really what kicked off this process. So for the last two years, up until February of this year, we’ve been working on this with the people on the working party.
One other thing I should add is that as I went through this, I began to realize that in many ways, some of the things I’d originally been talking about in terms of systems biology, would now, in my opinion, go into the category of synthetic biology, which is why there is a whole section on synthetic biology [in the report].
So when you said your perspective was a little bit different than Sir Colin’s, was that really what the difference was „Ÿ this distinction between systems biology and synthetic biology?
[In the report], there’s a diagram that shows the interrelationship between systems biology and synthetic biology. If you look at the systems biology side of that, we say that a lot of systems biology has come out of engineering systems and signal theory, so when I was thinking about systems biology, I was thinking about the application of engineering science „Ÿ systems and signal theory, principally „Ÿ to the analysis of biological systems, starting right up at the physiological systems level right down to the genetic level, the sub-cellular level.
So I certainly saw it in terms of engineering theory being applied to understanding these biological processes directly. The adjunct to that is that if you can understand the biological systems using systems theory and signal theory, which I believe scientists now would absolutely call systems biology, then that would give you an entrée into being able to design much better drugs, so I was actually thinking along those lines. Of course, Colin was thinking along similar lines, but in a much more sophisticated way, because I’m not a pharmacologist.
And then, the other part of that is that it seemed to me that … this could be very important for mainstream engineering, in terms of the computer industry, the telecom industry, etc. So that was the angle that I was coming at systems biology from.
Based on the findings, what would you consider to be the biggest challenges facing systems biology in the UK today? How do the recommendations in the report address those challenges?
The report is principally written for decision makers in the UK, and I would actually distinguish between the UK and US in this context because I think, for various reasons, in the US, there is a much more open-minded approach to this than there is in the UK. The principal reason for that is because I think the decision makers in industry, business, and government in the US have already basically woken up to the importance of systems biology. Whereas I think in the UK that is not really true. I think it’s true within drug companies, I think it’s true within areas of academia, but I’m not sure that the government has woken up to this yet. And not only the government, but what we call the research councils „Ÿ the equivalent to the NSF and the NIH [in the US].
Now, both Colin Dollery and I feel that this whole area of systems biology, and I would link synthetic biology into that as well now, could actually produce what we would call a third industrial revolution. So this is incredibly important, as we see it, for the British economy. It’s important for other countries as well, obviously, but the report is primarily focused on decision makers in the UK. And we wanted to do the work and write the report to try and influence the government and polarize industry in the UK „Ÿ because we have a strong pharmaceutical industry in the UK „Ÿ to take systems biology very seriously.
There are differences in approach between, let’s say, the US and Europe. In Europe the approach is more one of government investment to kind of kick-start a fundamental area. So we are trying in the report, and by lobbying now, to get the government to invest in this area.
Now, one of the key reasons for that from an engineering point of view is that the UK missed out completely on the microchip revolution because the professionals in the field didn’t apply enough pressure on the government to say how important this field was, and by the time the government woke up to this it was too late. We’re trying to avoid that in terms of systems biology.
So in terms of the recommendation, [one is] an investment of £325 million, which is frankly not a great deal of money, even for the UK. But we see it as being absolutely key to establish three to five centers for systems/synthetic biology, based on major British universities. The idea here is that there is no way that would represent an investment that would start this from scratch, but we’ve got some very good universities in the UK, and if the government invests in those universities, we can leverage the installed base of those universities to make us, from a research point of view, internationally competitive in this area. The adjunct of that is we believe we need to train a new type of engineer or scientist „Ÿ a systems biology engineer or systems biology scientist. So there are these two themes running in parallel in the report „Ÿ the research and the education.
There are already several systems biology centers in the UK funded by the Biotechnology and Biological Sciences Research Council [BioInform 09-02-06 and 01-19-07]. How would the centers that you are proposing differ from those, and how do you envision them working together?
The idea is that the centers we’re proposing would certainly work with, and, to some extent, complement what the BBSRC is doing. The difference is that in terms of the remit, the BBSRC has absolutely focused on the cellular and subcellular levels, whereas what we believe „Ÿ and an important member of our working group was Dennis Nobel from Oxford, who is an internationally famous physiologist „Ÿ we are all convinced in our working party that you have to apply systems biology at the physiological systems level, the level of tissues and organs and joints, as well as the cellular level. The point is that the BBSRC [centers] only do the cellular and subcellular levels, while there are these important, what I’d loosely call higher levels, that they don’t cover at all. And they certainly don’t have anything to do with engineering applications, because it’s a biology research council. And we see those areas as being very important.
Now that you’ve made these recommendations, what are the next steps? How do you plan to ensure that this funding is made available?
Prior to actually publishing the report, we — primarily myself and Colin Dollery — went together to the various research councils and got their views on this as we were writing the report, so certainly the report aligns with the view of the research councils in general.
So what we’re doing now is going back to the research councils and, on the basis of the report, we’re working on a strategy whereby we can then apply pressure through the research councils and directly on the government. The point is this needs to be new money, so it’s not just a question of taking money out of existing pots within the research councils and putting it into a pot for systems biology. We’re saying that the UK treasury needs to put £325 million of new money into this area, and we’re applying pressure via the research councils but also via various government agencies, and ultimately, hopefully perhaps talk to the Chancellor [of the Exchequer], Gordon Brown, about putting money into this.
What would you say is a reasonable timeline for getting that funding approved?
I would hope to get the funding put in place within the year. We’re talking about various universities making applications to get this money, and I would hope that by this time next year, that whoever the agency is who does this would actually be putting out a call for proposals, which would be a kind of three to four month lead time, with a view to getting funding in place by the summer of 2008.
Was there anything that you found surprising or particularly interesting in the course of this study?
One thing I would bring out would be the whole area of synthetic biology, or synthetic biology engineering. This is actually taking an engineering approach to producing biologically based standard parts, devices and systems „Ÿ so actually building biologically based machines using engineering principles.
Now, when we started doing this inquiry, I would say those ideas were at a very embryonic stage. The reason I’m mentioning this is that a lot of people have said to us that much more money is going to go into systems biology via the pharmaceutical industry, and potentially governments, than will go into synthetic biology. Now, I absolutely don’t believe that’s the case because the applications of synthetic biology are really direct mainstream engineering applications, like new materials or novel ways of producing sensors, et cetera. And it certainly is my view that if international industry sees that there are real applications in this area, which I think they will, then the amount of funding that will go into synthetic biology could be enormous, because they would see a return in terms of products, et cetera. So I think it’s misleading to say a lot of money is going to go into systems biology. I think it will, but I think equally a lot of money could go into synthetic biology.
It does seem that most of the applications that people talk about for synthetic biology have been more around engineered organisms for industrial bioprocessing or other biotech areas, but I guess there is a whole other aspect to it in mainstream engineering.
Just to give you an example of this, we built an oscillator „Ÿ it’s a fundamental building block in a computer because it’s basically the clock in a computer. Now we built last year a biologically based oscillator that you can control in terms of amplitude and frequency. So that represents one key building block in producing a biological computer. The Swiss Federal Institute of Technology in Zurich has produced an AND gate. So once you’ve got an oscillator or a clock and you’ve got an AND gate, you have the fundamental building blocks for making a computer, but this is a biologically based computer.
So the idea here is that instead of monitoring biological processes by using standard computers or standard electronics that kind of plug into the biological world, in principal it should be possible to build a biologically based computer that you can integrate into the biological [system] and maybe introduce into cells. But they’re based in biology so they can simply sit within a cell and count the number of cell divisions or whatever.
Now, the timescale of their operation would be incredibly slow by comparison to normal Pentium 4s, but that doesn’t matter because the point is that the environment in which they sit and the processes that they’re monitoring are also very slow. So these are very exciting areas.