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Profile feature – Margaret Craig

Profile feature – Margaret Craig - 7 January 2013. Clyde Biosciences

A new system to improve drug discovery has won its creator a major entrepreneurship award. After utilising a BBSRC-RSE Enterprise Fellowship, now she aims to build a world-leading bioscience company.

What does your spin-out company do?

Clyde Biosciences produces both instrumentation and biological products which are aimed at the large pharma companies and contract research organisations for drug discovery purposes. We have novel technologies designed to pick up the preclinical stage toxic effects of drugs screened on normal heart physiology.

Dr Margaret Anne Craig has founded Clyde Biosciences Ltd. to commercialise drug toxicity innovation. Image: Hamish Scott-Brown Photography.
Dr Margaret Anne Craig has founded Clyde Biosciences Ltd. to commercialise drug toxicity innovation.
Image: Hamish Scott-Brown Photography

Why heart physiology?

All new compounds going through the screening process are tested to ensure that they don't upset normal electrophysiology of the heart, or cause arrhythmias [abnormal rhythms] that could be life threatening. That's not just heart drugs that's all drugs, no matter their target, are tested this way.

Novel compounds will go through extensive preclinical testing and then at clinical trials around 40% fail because of toxicity to the heart. The whole drug discovery process takes 10-12 years and costs around $1.2Bn per drug, but the success rate to late clinical trials is about 3-5 compounds out of 5-10,000 potential drugs, so that's a huge expense, especially with late-stage clinical trials.

At that early stage there exists the opportunity to remove failures in the process such that they are not taken too far down the development pipeline. Technologies exist to detect cardiac toxicity but they have many limitations.

What technology is Clyde Biosciences founded on?

We have a novel instrument called CellOPTIQ which optically measures true transmembrane cardiac electrophysiology in cardiac cells using voltage sensitive dyes. This is a platform that can be used on adult heart cells, animal cells, stem cells – no other platform exists that can do that on the market.

A strength of our system is that normal electrophysiology of single heart cells is very labour intensive – it needs highly skilled people, is very time consuming and the number of tests you can do in a day is very low. We have a long history in Professor Godfrey Smith's laboratory at the University of Glasgow measuring the electrophysiology of single cells, and whole hearts. We realised we could apply our knowledge to design a much needed platform for drug discovery.

How does it work?

The dye is loaded into the cell and then we measure the change in voltage across the cell membrane. For a heart to contract, an exchange of ions takes place across the membrane of each cell which results in a change in voltage. This change in voltage is called an action potential and has a characteristic shape and parameters – CellOPTIQ detects these changes in voltage and we have also developed proprietary analysis software that that determines all parameters of the action potential.

What is the dye?

The dye is called Di-4-ANEPPS which sits in the membrane of the cell and responds to minute changes in voltage. The advantage of our system is that other technologies such as microelectrode array measure electrical activity in the solution outside of the cell and it is more difficult to interpret what's happening in the cell membrane. Also, CellOPTIQ is cheaper, easier to use, and provides more highly relevant data.

What else makes up your system?

We also write our own software. Action potential changes are millisecond events and data has to be sampled 20,000 times per second. We have software to acquire and interpret the data, which has been developed by Dr Francis Burton, who is a cardiovascular physiologist as well as an excellent software engineer.

Was there a 'eureka!' moment to your discovery?

Margaret Craig with (left-right) Professor Godfrey Smith, Dr Francis Burton and Professor Jon Cooper. Image: Hamish Scott-Brown Photography
Margaret Craig with (left-right) Professor Godfrey Smith, Dr Francis Burton and Professor Jon Cooper.
Image: Hamish Scott-Brown Photography

I've worked here 13 years and over time been involved with developing biological products such as arrhythmia assays, cell preservation solutionsand instrumentation. Following our studies with the whole heart we wondered if we could do similar methods in single cells. When we got the idea we always assumed it would be possible in 2-3 years.

We managed to access funds from the university's Challenge Fund which allowed us to buy equipment and build a prototype. This instrument cost tens of thousands of pounds to build, and we're pitching instrument sales around at £180,000. We have spent time validating the system and we have we just finished drug screening study with GlaxoSmithKline using a type of cardiac stem cell called induced pluripotent stems cells, or iPSCs.

And how did BBSRC funding help?

Both my colleagues Godfrey Smith and Jon Cooper, Professor of Bioelectronics and Bioengineering here at Glasgow, have both had BBSRC grants to look at measuring electrical activity in single cells.

And you then applied for a BBSRC-RSE Enterprise Fellowship award?

I had returned to the commercial work for three months and our commercialisation manager at the University of Glasgow told me about the scheme and here suggested I applied for it. I didn't know about the award until he mentioned it but I applied and was delighted to get a place on the programme.

And what did it enable you to do that you couldn't before?

It gave me a whole year of salary to work on this and nothing else! And also gave me business training for 2-3 days a month which was great taking part in everything you need for business: how to set up a business, sales and negotiations, getting investor ready, and you're working with and networking with the people that are essential to building a business. This was based at the GO Group based in Glasgow as well as the Royal Society in Edinburgh who also fund the fellowship scheme. Lots of people I met then are still helping and guiding me in intellectual property (IP) matters, as well and the legal side for example shareholders agreements. It's a really broad introduction which was great.

Were you interested is business before?

I never knew anything about it or thought it was something I'd find myself involved in, but I love it and I don't think I could do anything else now.

How did it feel to get the £40,000 Royal Academy of Engineering ERA Foundation Entrepreneurship Award?

Great! I only knew about the award from about two weeks before the closing date, but I worked over an intense weekend to get the application completed. I got shortlisted and the university prepared me by carrying out a mock interview in Glasgow. I was not looking forward to going to London and facing the panel of eight engineers, some of whom were also serious businessmen. There were five other candidates but I got the unanimous vote.

It was a great awards ceremony with 400 people, at the Royal Opera House in Covent Garden. It was quite daunting – the other candidates included people who'd been in charge of Olympic delivery, a bridge designer who made one between two Scandinavian countries, the designer of the Range Rover Evoque…

Craig collects the £40,000 Royal Academy of Engineering ERA Foundation Entrepreneurship Award at a gala event. Image: Royal Academy of Engineering
Craig collects the £40,000 Royal Academy of Engineering ERA Foundation Entrepreneurship Award at a gala event.
Image: Royal Academy of Engineering

What did people make of your invention in such company?

The technology has received a lot of interest and people realised that this was a way of working with stem cells, and reducing the amount of animals used in research. Then of course I was standing there as a woman too, which many commented that it was great to have a women winning such an award. In my experience I think it's tougher for a female than for a male…

… in business as well as in science?

Yes both. However, I am now working with a Scottish Government Committee to look at ways of addressing issues for women in science and business.

After such a prestigious award, what does the near future hold?

Because it is a platform to measure electrical activity, via changes in fluorescence, it means that we can alter the optics so that the system can be used to detect other parameters such as calcium changes. It could also be used to carry out toxicology screening on more than one cell type such as neural cells.

Have you tried it in other cells?

We're now negotiating with the company Cellular Dynamics; they produce the best cardiac cells and neuronal cells internationally. We've just been to Phoenix in the US to see them and will be presenting work with them at a major conference in March 2013. They have received £70M of investment, and we have some investment from the IP Group and have new premises too.

When did you first become interested in science?

I was interested in science from high school stage, especially in the human physiology. I graduated from university with a degree in Immunology and Pharmacology. I then carried out an MSc and PhD during which time I had two children which was very hard going.

Now I have a major job to do in that I am setting out to build a world-leading bioscience company. No easy task!