On the industrial front
If it is possible to link the words ‘sexy’ and ‘industrial biotechnology’, biofuels is the conjunction. Just about every country on the planet is looking for alternative fuels and Paul Tuckley, Auckland-based trade development manager for UK Trade & Investment, is interested in Agrigenesis spinout Biojoule (Unlimited Future May 2006). “In Scotland,” says Tuckley, “they are running a power plant on the same sort of willow tree, but [the technology] hasn’t been applied in the same way as Biojoule has in the production of ethanol.” Tuckley adds that the UK’s Argent Energy, set up in 2001 to turn tallow into biodiesel, is researching building a plant in Waikato to bring the process here.

As with human pharma, creating biofuels could mean a huge payoff; but it takes a lot of space and money to produce enough to make a difference to global fuel needs.

There are other industrial biotech avenues to head down. NZTE’s Lyn Bridger has identified 150 New Zealand companies involved in industrial biotechnology. “I’ve had to get people’s minds away from biofuels; the minute you mention industrial biotechnology, it’s automatically biofuels. A lot of our capabilities will be found in other areas of our toolkit.”

One of the companies topping Bridger’s list is BioDiscovery. The company (and its land-based collaborators on both islands as well as marine-based NIWA) searches the New Zealand environment for organisms with unique molecules that can be isolated and developed into biopesticides and other agricultural chemicals.

Andrew Broadwell is a director and co-founder of the Auckland-based company and says other groups worldwide are doing the same things. “Everybody is looking for solutions to the same problems and you don’t know what you’re going to come up with. Because we have unique plants and unique microbes, it’s worth looking here.”

While others around the world are also looking, Broadwell says BioDiscovery is one of the few private companies involved in searching for agriculturally active molecules. The others have gone out of business, he says, and that creates an opportunity for BioDiscovery. Why won’t it fail, too? The company started in 1994 and while government funding has helped, the fact that it’s cheaper to run a small company in New Zealand than in other parts of the world has been a major factor in its success to date, Broadwell says. BioDiscovery is true to its ‘discovery’ tag and, when bioactive compounds are isolated, partners with commercialisation companies and generates royalties from the work. Broadwell says there are quite a few compounds under investigation, but none have yet hit blockbuster status.

When it comes to human pharma, people usually focus solely on the US, but when it comes to industrial, agricultural, marine and horticultural biotechnology, New Zealand starts to look attractive, says Tuckley. Our status as one of the world’s fastest growing biotech industries is also appealing. “Ten years ago, New Zealand wouldn’t have been on the radar, outside of its universities,” he says. “Innovations in farming and pastoral management were always well respected but have really come forward in the last ten years. And it’s not just focusing on how grass grows, but making it grow to give more nutrients to animals. That’s of tremendous interest worldwide, but particularly to the UK where a lot of the traditional farming methods originated from.”

Tuckley sees it as a two-way street. “Dealing with New Zealand is good for us. On the other hand, dealing with the UK for New Zealand companies, there is a cultural heritage and the UK is the largest bioscience country in Europe by a long way. Tying up links with the UK is an ideal way into Europe. I think that’s a good benefit for New Zealand.”

The UK isn’t the only country showing interest in our biotech strengths. Bernard Gilly, a French venture capitalist and partner at Paris-based Sofinova Partners, visited New Zealand in April. Prior to the trip, he admits he had a “criminal tendency” to believe nothing was going on in our part of the world, but the trip left him excited. He discovered there were things of interest for him in New Zealand and is in negotiation with at least one company.

The European Commission is also keeping a close eye on New Zealand’s achievements in agriculture, food and biotechnology. Christian Patermann, the director of biotechnology, agriculture and food research for the director-general of the European Commission, says his first memory of New Zealand was eating salted butter as a child. Patermann, a World War II baby who grew up in Germany, had never seen the stuff before; what impressed him most was the innovation behind it.

Touring New Zealand last month with a delegation from the European Commission, Patermann says New Zealand’s isolated situation provides a treasure trove of biodiversity not found in other parts of the world.

“You also have a very high standard of research and a very interesting landscape of partnerships of public and private institutions. The CRIs, for example, are very unique and very interesting for us. You are very small, but very dynamic. But you have limits, there’s no doubt about that.”

What are those limits? A small population of just over four million people is a major factor. The answer for our biotech success, according to Patermann, is to spend time finding the right priorities and allegiances. “Where are you strong? Where can you be stronger? You are a country determining its future and it is an art to find the right solution.”


Raising chickens

When we get an infection or a disease, our immune system produces specific antibodies to fight it. Other animals produce antibodies specific to whatever diseases they may contract, too. In some treatments for cancer (like the breast cancer drug Herceptin) and autoimmune disease, monoclonal antibodies that are specific to the human disease are grown in specialised hamster cell culture systems. These techniques are expensive, inefficient and require the sacrifice of animals.

San Francisco-based Origen has developed a way to switch the chicken’s immune system so that it produces human antibodies instead of chicken ones. And it has not only developed a way to make human monoclonal antibodies, but also polyclonal antibodies (monoclonal antibodies bind to a single site on a disease; polyclonal antibodies bind to many sites, making them much more powerful tools). Furthermore, Origen has developed the technology so that the antibodies are deposited in the egg white and that comes in neatly packaged easy-to-harvest eggs.

Having never laid an egg, I’m unaware of any discomfort involved. But it’s got to be better than the steps required for conventional cell culture: having your ovaries removed, being forced to grow a tumour or having your blood harvested.

Origen’s platform is impressive in a few other ways, too. First, compared with conventional monoclonal antibodies, the ones in the eggs are enhanced, says Origen founder Bob Kay, which causes the immune system of the patient receiving the drug to fight the disease much more effectively.
Second, the antibodies can be produced for approximately one-tenth the cost of those from conventional systems (as a start, according to innovation and technology publication Red Herring, Genentech recently paid US$408 million for a cell culture production facility. “With the chicken,” says Kay, “we believe that for less than $20 million we can set up a facility that can produce the world’s need for a particular drug). Third, the ability to produce polyclonal antibodies opens a new class in human therapeutics.

“[Biotech companies] have become very efficient at generating potential drugs and many companies have ten to 20 antibody [candidates] sitting on the shelf,” says Kay.

Each drug sitting on that shelf, he says, will cost US$10 million to US$15 million to develop to the point of clinical trials and companies simply can’t afford to develop all of them. With fingers crossed, they choose one and hope they’ve picked the winner. But there are a lot of failures, and if Origen can lower the cost from US$10 million to US$1 million then, instead of having one shot at goal, a biotech company can afford to have ten shots.

So one ambition for Origen is to help other companies get more drugs into the clinic, which will increase the chances of finding a really good therapeutic. And, because the antibodies are enhanced, their cell-killing abilities are stronger, making the ones that are successful even more potent. But it is the ability to make polyclonal antibodies that could be the proverbial golden egg.

Kay, who was born in England but immigrated to New Zealand in 1965 at age 14 (his father assumed the role of head of electrical engineering at the University of Canterbury), went to Christchurch Boys High and then completed a PhD at the University of Otago in biochemistry. Following that, he spent four years on a research fellowship in England and then went to Boston where he spun out his first biotech company from the Harvard Genetics Institute. After he took that public, he moved to California and started his second company, which used mice to produce human monoclonal antibodies. When that company was acquired by Medarex (another US biotech company), he began working on the platform that became Origen.

Origen’s intentions should be taken seriously: it was among the 200 companies shortlisted for the ‘Red Herring 100 North America’ — an annual award given to new and innovative technology firms. It has also already raised US$15 million over three rounds of financing (US$6 million of that from National Institute of Health research grants) and last month its technology was featured in the prestigious journal Nature.