Blue dye liquid disperses against a white background

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Chasing the blues

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The hunt for a naturally occurring blue – something that is surprisingly rare – has led a collaboration of researchers and a biotech firm to an unlikely source – algae.

Blue is one of the rarest colours in the world. To see why, visit an art gallery.
For centuries Western art lacked a true blue in its paintings – the Romanesque and Gothic wings of galleries are rather blue-green affairs. And then, suddenly, techniques and rare blue minerals used by Buddhists in Afghanistan were imported into 14th century Italy.

At a stroke, blue – or ultramarine as it was known – became the most sought after and highly prized colour in Renaissance art. Its scarcity and price made it the colour of royalty and the divine.

Blue has remained in high demand for all kinds of products ever since. Yet due to its scarcity in the natural world – most of the blues we see in nature are actually elaborate optical illusions – supply has never been able to keep up.

A natural true blue from which pigment can be extracted is still exceptionally rare.

This may be hard to believe when the colour is found in everything from Smarties and soft drinks to cosmetics and textiles. Artificial colourings have helped meet the demand, but these are unpopular with today’s consumers who are increasingly conscious about what goes into the things they buy.

This change in buyer behaviour has generated unprecedented demand for natural colourings that can perform well across a range of applications.

How then, do you create a true blue from a world lacking that colour in its natural palette?

Bluebells in flower in spring in a garden

In 2012 a fledgling Scottish biotech company partnered with a group of University of Edinburgh scientists to explore how a natural blue colouring can be cultivated and extracted from blue-green algae.

The collaboration has gone on to make pioneering breakthroughs, enable significant company growth and sustain a thriving partnership with the University that continues to expand into new areas.

It has even been responsible for helping create blue booze. A partnership with Leith-based drinks producer, Firkin Gin, led to the launch in August 2017 of a natural blue version of their gin – Firkin Blue – which currently retails at $438 per bottle.

True blue

Artificial blue colouring of the kind you might find in sports drinks and children’s sweets is known as Brilliant Blue, but on close inspection it’s anything but. A petrochemical by-product, Brilliant Blue is a cause of significant consumer concern in today’s health-conscious culture, hence the push to find a more natural alternative.

A pile of blue sugar covered sweets

One source of non-artificial blue colouring is phycocyanin, a pigment-protein naturally produced in blue-green algae known as cyanobacteria. The main method of phycocyanin cultivation involves cyanobacteria being grown in vast, shallow outdoor ponds to enable photosynthesis. But this process comes with all the common problems that are inherent to an agricultural manufacturing method – competition for space and fresh water; exposure to contamination risks; reliance on unpredictable weather systems; and security issues.

In short, the established system for cultivating phycocyanin is far from the reliable, efficient and predictable process required to cope with an ever-increasing demand for natural blue colourants.

However, a colourful collaboration was about to change things.

In 2012, University of Edinburgh molecular biologist Dr Andrew Free was investigating how communities of microbes could be used to do important environmentally related tasks when he was put in touch with David Van Alstyne, Founder of Scottish Bioenergy, an early incarnation of what would later become biotech company ScotBio.

Van Alstyne wanted to explore the potential uses of phycocyanin, and Free, who had not engaged with industry before, was interested in the possibilities this project held.

The pair wasted no time in recruiting PhD student Rocky Kindt, who was put to work analysing samples taken from photobioreactors – fermentation vats fitted with specialised lights – in which algae biomass was being grown under a variety of conditions.

“We wanted to understand some of the microorganisms living in those reactors,” says Free. “We wanted to see how those organisms interacted with the cyanobacteria – the blue-green algae – to either help its production of the pigments that the company wanted to produce, or in some cases were perhaps hindering its growth and production of the pigments.”

Algae floating on water surface of a canal

Materials and equipment from the lab of Newcastle University’s Dr Gary Caldwell, another ScotBio collaborator, also facilitated this initial work.

Kindt was enthusiastic about the work he and Free were doing with ScotBio. The interplay between academic research and industrial need was a big part of that appeal.

“I was very much attracted by the exciting routes toward having real world impact,” Kindt says. “It was interesting to work from the company’s angle too, in terms of trying to understand these discoveries and how they could be realised in a commercial application.”

Kindt’s passion and expertise made him an appealing hire prospect for ScotBio, and upon completion of his PhD he was offered a job with the company. He now heads ScotBio’s R&D arm and is Chief Technology Officer.

Reflecting on the partnership’s successes to date, Kindt credits Free and the early work conducted in his lab with setting the scene for ScotBio becoming the company it is today.

“It was through Andrew Free’s support and his laboratory that we were first able to understand how to handle this material and the complex processing chain towards getting a purified blue material out at the other end,” Kindt says. “The access to expertise, facilities and resources at the beginning made possible the fundamental things that led to ScotBio growing, getting funding and being where it is today.”

By 2015 the research team had developed a patented, containerised system for cultivating phycocyanin, the natural blue colouring. While the traditional system cultivates algae in exposed, open ponds and relies on sunlight to photosynthesise the cyanobacteria, the team’s closed, controlled containers were fitted with specialised lights to replicate the sun’s rays. This provided a level of traceability, security and reliability of supply that had never been possible before, and would be highly desirable for brands making the move to using natural colouring in their products.

Gloved hand holding cyanobacteria in a petri dish

ScotBio was keen to scale up production so that it could supply its natural blue colourant to a ready and waiting commercial market. At this stage Dr Alistair McCormick, then a new Chancellor’s Fellow at the University of Edinburgh, was introduced to the partnership by Edinburgh Innovations, the University’s commercialisation service, to maximise the yield of phycocyanin and bring them closer to commercialising their discovery.

Blue ribbon

McCormick’s first move was to secure a proof-of-concept funding grant from the BBSRC NIBB Phyconet, so that he could explore new ways of purifying phycocyanin using a highly specialised and targeted filtration method called chromatography. This approach proved extremely effective, yielding a hitherto unachievable level of purity, and making the partnership’s phycocyanin suitable for the pharmaceutical, nutraceutical and therapeutics markets.

The commercial returns on purity are significant, according to McCormick. Food grade level phycocyanin is available for quite a low price, but one gram of analytical-grade is phycocyanin is worth around £100,000.

In addition to this breakthrough, which significantly enhanced the company’s commercial prospects, McCormick created a molecular toolbox for engineering cyanobacteria. Now available to buy, the tookit allows potential applications for microalgae to be investigated by academics across the world.

In 2019, the partnership won the prestigious Innovative Collaboration prize at the Scottish Life Sciences Award for their pioneering collaboration. The company is now in a strong position in the rapidly growing market for natural food and drink colourants, and in the pharmaceutical and nutraceutical markets.

3 doughnuts on a counter, two will blue icing and one with white

“The partnership has allowed a small company to really punch above its weight in terms of the types of challenges it could dare to try and overcome,” says Kindt. “We’re able to distinguish ourselves from our competitors in offering something that is scalable, predictable, and can be deployed anywhere in the world.”

New horizons

New projects and plans between the University and ScotBio are underway. ScotBio is in the process of expanding its manufacturing facilities. It has been awarded funds from Medical Research Scotland and the Industrial Biotechnology Innovation Centre (IBioIC) for a new collaboration involving McCormick and Dr Richard Sloan from the Infection Medicine centre within the Edinburgh Medical School.

The project will investigate the antiviral and antimicrobial bioactives that are naturally present in cyanobacteria, with an aim of discovering new therapeutic treatments for viral diseases.

A partnership that began as a search for true blue is now broadening the spectrum of its activities.