The four colours of biotechnologyy

The UK Government has decided there might be money in biotechnology. As well as this, in a few weeks, the spotlight will be on what the world's most Northern scientific community can offer the biotech community with the 4th International BIOPROSP Conference on Marine Biotechnology (Norway). However, these developments have nothing to do with the human genome, monoclonal antibodies or biomarker-based diagnostics, as the biotech universe extends far beyond the biopharmaceutical advances — and setbacks — that hit the headlines.

Susan Aldridge

The biotechnology sector is occasionally described as a rainbow (with some colours missing) with each subsector having its own colour: red biotech is the medical sector, white (sometimes known as grey) the industrial sector, green is plant and environmental biotechnology, and blue is marinebased biotech. The term 'black biotechnology' is sometimes used to describe activities related to bioterrorism.

All the sectors of biotechnology have something to offer the pharmaceutical industry. Big Pharma is using red biotech to fill its dwindling pipelines, which is all the more important as its 'patent cliff', a term analysts use to describe the unprecedented loss of patent protection drug makers face during the next few years, looms ever larger. According to a Datamonitor survey conducted in 2007, companies can expect to lose $140 billion (108 billion euro) in sales up to 2016 as their blockbusters face increasing generic, including biogeneric or biosimilar, competition. Therefore, pharmaceutical companies need biotech innovation from drugs hitting novel targets and pathways, such as RNA interference, therapeutic vaccines and even gene therapy. Hundreds of products similar to this are being developed in small biotech companies and academic departments worldwide. These SMEs need Big Pharma's cash and expertise to push their programmes towards the clinic, and so we can expect a steady stream of deals going forward into 2009.

The application of white biotech to pharma may seem a bit less obvious. EuropaBio (the trade organization for the European biotechnology industry) defines white biotech as the application of biotechnology for the processing and production of enzymes, chemicals, materials and bioenergy. Much of the new interest in white biotech comes from the global drive towards a lower carbon, more 'knowledgebased' economy — both to try to alleviate global warming and to go easier on the earth's finite resources. Until now, the chemical, plastics, pharma and healthcare industries have been overwhelmingly fossil fuel based, both in their power sources and their production processes. This cannot continue. A big focus in white biotech is to find efficient ways to manufacture biofuels to replace fossil fuels. The other goal is to replace conventional chemical processes, including those using metal catalysts, with lower energy, cleaner, enzymebased processes.

As mentioned previously, the UK government is taking an interest in white biotech. It has set up the Industrial Biotechnology Innovation and Growth Team, which is looking at the opportunities and challenges in this area. A policy document will be published later this year, setting out a strategy on white biotech.

For the pharma industry, white biotech is well aligned with 'green chemistry' initiatives to make drug manufacturing processes leaner, cleaner, with less waste and toxics production. There is probably an enzyme for every chemical transformation you might want to do in assembling a drug molecule. The problem is obtaining that enzyme in the quantities needed for industrial processes. There are biotechnology companies, which include Biotec Pharmacon (Norway), Biocatalysts (UK) and Novozymes (Denmark), that specialize in doing just this — cloning a gene of interest, expressing the enzyme it codes for (and perhaps engineering it for better properties), scaling up production, and packaging and marketing it for the industry sector that can use it as a tool.

The author says…

The 'genetokilo' approach is the focus at the Centre of Excellence for Biocatalysis, Biotransformations, and Biocatalytic Manufacture (CoEBio3),¹ which is a consortium between the Universities of Manchester, Strathclyde, York and Heriot-Watt (UK). There is a wealth of research going on here into processes of interest to pharma, which is why AstraZeneca, Dr Reddy's, Merck and Pfizer are among the industrial affiliates of CoEBio3. Projects include methods for combinational biosynthesis of calciumdependent antibiotics (a new type of drug), with the identification of relevant enzymes on the biosynthetic pathway; the use of whole cell biocatalysts for the more efficient production of recombinant protein drugs; and biocatalysis in ionic liquids, which are of great interest as alternatives to toxic organic solvents in the pharma industry.

Many years ago, I wrote a story about the production of blue dye indigo from bacteria. This was to replace the conventional chemical production of this important product. In 2008, this is still not a viable large scale industrial process — although it is getting there. This is the challenge with white biotech; companies don't want to change their processes unless they are sure the biological approach can be scaled up and will work. This is where the National Industrial Biotechnology Facility (NIBF), sited at the Centre for Process Innovation in Redcar (UK), comes in. Opened last year and working in close partnership with CoEBio3, the NIBF is a 'test bed' where companies — and they have pharma companies among their list of clients — can manufacture trial quantities of a material or compound using a white biotech method to see if they can make a commercial case for large scale production.

One of NIBF's interests is in marine biotechnology, which brings us neatly into the blue biotech sector. Norway has a long tradition in fishing and exploiting the marine environment and, of course, it has plenty of oil. In recent years, attention has been shifting to bioprospecting — the search for compounds of value to the medical and food sectors in the deep waters of the country's fjords or in the more extreme environment of the Arctic. That is why bioprospecting, backed up with a wide range of genomics and molecular biology techniques, is becoming increasingly important for the world's most northerly university, the University of TromsØ (Norway). In February 2009, TromsØ will host a conference on bioprospecting where organizations such as the US National Cancer Institute will show their interest in this area in the hope that the sea might yield new cancer drugs.

Again, pharma needs to fill its pipeline. There is some disillusion with the output from combinatorial chemistry, which can produce millions of potential drug leads in one go, but has failed to reduce attrition rates. Organisms, particularly bacteria and small invertebrates that are adapted to extreme environments such as the cold waters of the Arctic, may be a better bet when it comes to finding the next blockbuster or, to be more realistic, high value drug. Biotec Pharmacon is also located in TromsØ and has built a company specialized in the production of enzymes that can deal with extreme environments. Unlike conventional enzymes, which are sensitive to the conditions under which they are used, those that can survive unusual conditions have something extra to offer and molecular analysis can show which features of a molecule are adapted. These findings can then be used as a basis for molecular engineering to produce designer enzymes for a range of processes.

There is no really obvious connection between the main area of green biotechnology, which is concerned with genetically modified crops, and pharmaceuticals. However, green biotech could use microbes and plants to clean up contaminated land and water. Such biological approaches could help industry deal with waste disposal.

And finally, to black biotechnology. In the wake of 9/11, the US Department of Health and Human Resources handed out several contracts to companies to mass produce vaccines against tularaemia, plague and smallpox, which are all thought to be potential terrorist weapons. In April 2008, the Cambridge (UK) company Acambis won a £213 million (€244 million) contract from the US government to supply smallpox vaccine. The cash injection will help them progress work on a vaccine against the hospital bug Clostridium difficile. Perhaps it's regrettable that a terror threat represents a business opportunity, but many patients could benefit in the end.

References

1. Centre of Excellence for Biocatalysis, Biotransformations and Biocatalytic Manufacture. www.coebio3.org

2. Fierce Biotech (2007).www.fiercebiotech.com/story/patent-cliff-looms-for-big-pharma/2007-05-02