In a series of three articles, BBSRC Innovator of the Year 2013 winners reveal the secrets behind their innovations.
In this, the first, Commercial Innovator winner Dr Anna Hine reveals the highs and lows of commercialising an elegant technique for building proteins from gene libraries which has been licensed by a major antibody manufacturer and could catalyse the development of many new therapies. In the second , Overall Innovator winner Dr Ryan Donnelly explains how hydrogel-based microneedles might be the future of safe drug delivery, and how they could be used for non-invasive blood monitoring. In the third , Social Innovator winner Peter Mertens recalls how his group helped prevent the bluetongue disease of sheep becoming endemic in the UK, saving the British economy an estimated £480M in 2008 alone.
How does it feel to win?
I was stunned! I was really pleased it's very good for Aston University and the people I work with. I thought the competition was very stiff I was very surprised to win.
How did it come about?
It all started with my particular interest in zinc-finger proteins (important structures that bind to DNA) and how they interact with DNA. I realised early on that this research, funded by BBSRC in 2001, would have reach beyond zinc fingers.
Can you describe your innovation in your own words?
Actually there are two, 'MAX' and 'ProxiMAX' randomisation, which are molecular technologies for protein engineering that have diverse applications in biotechnology and the pharmaceutical industry (such as antibody engineering). Some protein's amino acids are encoded by up to six codons (three DNA bases) and others by only one, so that bias and the huge numbers of combinations of DNA that can encode different proteins means you end up with enormous DNA libraries. And this bias becomes a problem when you express all your proteins that come out at different concentrations and the screening technology works on the basis that all proteins are at the same concentration.
Our invention got rid of the bias and the excessive size so we're just using 20 codons to encode 20 amino acids with no wastage. It's simpler, more efficient and much more accurate.
And because of the way we do it, we could go beyond that and ask for certain chemical characteristics in the protein – hydrophobic amino acids here, acidic ones there – in any combinations that you want, but all engineered at the DNA level.
What is the end impact of your product?
It makes protein engineering companies do a far better job, that's the primary impact, which in turn should lead to better biopharmaceuticals. It's already led to high-tech employment in the UK, which I'm quite proud about as well.
How does it feel to have a real product on sale?
I'm delighted! How many academics really get to make a difference? It's a privilege. It's something everybody wants to do, but the opportunity relies on so many things coming together. You need great scientists, you need the funding, the right company and you need a lot of luck as well. It came good for me.
How did you go about commercialising your innovation?
The first BBSRC funding for initial work was in 2001, and we got Follow-on Funding in 2005-06 which helped my colleagues Dr Marcus Hughes and Dr Mohammed Ashraf (then a PhD student) to develop ProxiMAX, the second invention. But the Follow-on Funding helped us to do some market research in the US and we found more interest in engineering antibodies than enzymes, which were the target of our first system. So without BBSRC funding we wouldn't have been going down right track, it helped us to establish that the interest was in the second venture.
What was the difference between your first and second venture?
MAX and ProxiMAX randomisation are two quite different techniques. The first one, MAX, had to be optimised each time you did it because new DNA sequences were needed each time. We formed a spin-out company in 2004 to exploit this.
The second, ProxiMAX, uses the same methodology whatever your target, which is much more efficient. When it looked as though the patents were going to be granted in 2011, 2012 and 2013 we licensed the technology to protein engineering Isogenica Ltd. who markets it as one of their services called Colibra.
Were you disappointed when the first company didn't work?
Not really – it was a bit sad because we'd worked hard but the company wasn't needed so we just cut its throat – we folded the company and discontinued the first patent, then concentrated on the second one and that's what we've had commercial success with.
Did you take any business training along the way?
I completed a Medici Fellowship over 2003-4 which was like a condensed 'all-the-things-you-could-ever-learn-if-you-could' course, but it was invaluable. Then I took an 18-month secondment into the Business Partnership Unit which is Aston's technology transfer office which was fantastic and taught me to speak science in plain English. I really enjoyed such a change, and experiencing the business attitude to science that was most revealing; far less the technical detail of 'how it worked' and more 'what are you going to do with it afterwards?'
And I love interdisciplinary work and this was extreme interdisciplinary!
And in the middle of all this you took time out to have a family?
Yes, I had two children in the middle of it that's why I didn't go to the US. I'd just had a second child on 2006, the first in 2003, and I've worked part-time since the first was born. It was a very good way of finding perspective.
How do you balance business, science and a young family?
I usually work Monday to Wednesday, and when I go home I do all the things mums do and there's no time for thinking about science. But then when I'm back at university on Monday it's all fresh. The balance is very fulfilling. I think I'm more productive part-time than I was full-time. You can get stuck in a problem and the best way to solve it is to walk away and come back a couple of days later.
Did you ever fear when you were away that you wouldn't be able to get back into it?
No. I think it's different for academics because even when I was on maternity leave I was in touch with my research group because it's not something you can get someone to cover you for.
How does it feel to be the first female winner of Innovator?
I am proud and delighted to be the first. I don't think I won it because I'm a woman, but I'm delighted I'm putting the balance right. I'm sufficiently young to have never experienced any sexism in the work place or my education.
What inspires you to do science and take it into the commercial world?
That's an easy question. When I was post-doc at Harvard Medical School in 1993-94 I watched the science take place that led to the development of Thermo Sequenase, the enzyme used in first-generation DNA sequencing for the Human Genome Project. I walked into the lab one day and the scientist concerned had a very big grin on his face, because he knew what he'd done. He was researching a rather dry question, but with a bit of work on the application… it was very exciting.
What was it about that discovery that rubbed off?
Er, cash? Ha ha! Not personally for me but I saw what difference it made. Making a discovery like that put cash out of the equation altogether, because the inventors could then do the science they liked, just because they liked it. The invention made lot of money for the researchers, the lab and the university.
Are you motivated by money?
In part, you can't do commercialisation unless you'd be pleased to have the money, but that's not the whole story. When I received the BBSRC Commercial Innovator Award what I was really pleased about is that I'd done something that made a difference.
Isogenica was founded on a protein library screening technology called CISDisplay, which is a powerful screening technology, but until accessing our innovations they had to buy in their libraries from abroad. Now they can make their own libraries, and they can also sell libraries to other people, so it's brought manufacturing to the UK and led to exports and the considerable expansion of Isogenica. A lot of current therapies, such as Herceptin and Avastin, are antibody therapies so I hope that by making better libraries the pharma companies will find better hits and as the public we'll get better drugs down the line.
Can you use your technologies in applications besides antibody therapies?
Not yet in practice, but the technology works for peptides, which we're starting to do at a research level, and for enzymes and protein scaffolds. Isogenica's work has taught us more about T4 Ligase, which is one of the backbones of molecular biology. But we're also engineering antibacterial peptides that also have insulin-releasing properties. We have other projects going too but I can't talk about those.
What made you get into science?
When I was 12 or 13 I saw a TV programme about a little boy ('The Boy David', David Lopez) whose nose and face had been eaten away by visceral leishmaniasis. And I recall thinking "surely you should be able to grow new flesh, new tissue…" That got me interested in science and biology, and then I got more interested in genetics and molecular biology. I remember going on early university visits and saying that tissue engineering (as it's now called) was what I wanted to do and being poo-pooed. Back in the mid-80s they said it wasn't possible but it was definitely the point I decided I wanted to be a scientist.
The UK has perhaps the richest history of scientific innovation of any country in the world, and the Royal Society report The Scientific Century: securing our future prosperity shows that innovation and commercialisation are flourishing in Britain.
For example, from 2006-10 university spinout companies have floated on the stock market or been taken over for a combined total of £3.5Bn and employ 14,000 people in the UK. Furthermore, between 2000 and 2008, patents granted to UK universities increased by 136% and university spin outs had a turnover of £1.1Bn in 2007/08 (ref 1).
The perception that the UK is not successful when it comes to commercialising science, or as some have put it: "Britain invents; the world profits" is therefore clearly outdated, and that strategies to harness and increase innovation are working.
In addition to the benefits it brings, it is argued that present £7.5Bn science budget pays for itself many times over as technology is developed and then taxed as it is sold. The Medical Research Council estimates every pound it spends brings a 39p return each year (ref 2). Moreover, independent studies have shown that for maximum market sector productivity and impact, government innovation policy should focus on direct spending on research councils (ref 3).
Finally, the UK produces more publications and citations for the money it spends on research than any other G8 nation. Specifically, the UK produces 7.9% of the world's publications, receives 11.8% of citations, and 14.4% of citations with the highest impact, even though the UK consists of only 1% of the world's population (ref 1).