In the second part of our series on genetic engineering, CARROLL DU CHATEAU looks at why GE pharmaceuticals get the thumbs up and GE foods the thumbs down.
The symptoms of cystic fibrosis are relentless. First come the recurrent short-term infections, then the bronchiectasis, moving ultimately to a fully-fledged lung-destroying condition. In 95 per cent of cases the disease also attacks the pancreas causing gut malabsorption and malnutrition. The worst aspect of this, the most common lethal genetic disorder in New Zealand which routinely kills people in their mid-20s and 30s, is the fear of not being able to breathe. It haunts the eyes of sufferers.
Which is where the field trial on sheep, genetically engineered to produce a medicine to fight cystic fibrosis (and possibly emphysema) in their milk, comes in. The trial, in association with PPL Laboratories in Edinburgh, Scotland, where Dolly the sheep and the first set of piglets were cloned, is under attack from the Green Party.
Green MP Sue Kedgley says, "It would be a gesture of faith to a concerned public if AgResearch and other New Zealand research institutes withdrew any pending applications for field trials."
This trend in New Zealand is in contrast to the climate in Britain and North America where public response to GE pharmaceuticals has been much more favourable than for GE food.
There, the difference in attitude comes down to two factors. First, choice. At a fundamental level people want control over what they put in their mouths. In the case of GE food, they were outraged that often-unlabelled genetically engineered ingredients were slipped into ordinary, well-established products such as baby food. With medicine, however, people will often take a calculated risk - better health versus the possibility of side-effects.
Second, relative safety. As Dr Jim Watson, microbiologist and chief executive officer of Genesis Research the only discovery-based biotech company in New Zealand, says, it is all to do with the US Food and Drug Administration.
"The FDA has international recognition," he says. "The reason the world accepts new drugs, especially those that are genetically engineered, is because of the testing procedures. Yet for GE food there was no testing. That's really the heart of the problem."
Over the past 30 years the international biotech business, which is based on genetic engineering, has grown hugely. In cities such as Cambridge, England, the university is surrounded by satellite science parks, many of them owned by Cambridge Colleges. Here, in manicured splendour, scientists, and often university professors, work with the well-funded private sector businesspeople to produce new GE technology that will help in the fight against disease.
In North America the industry is even bigger. Breakthroughs are coming all the time. Already insulin, instead of being extracted from the pancreas of animals, is made by putting a human gene into bacteria, cloning it and producing insulin. Genetic engineering is used to treat human dwarfism, renal failure and haemophilia. The litter of cloned piglets from the Roslin Institute just outside Edinburgh, is just another step towards made-to-order organs for human implants. The next step will be clones engineered to produce transplant organs where, say scientists, potentially harmful genes will have been "knocked out."
And although it will be brave people who agree to have these new organs implanted, some when faced with death, probably will.
Wouldn't you welcome some replacement neurones, genetically engineered from a scraping of skin cells from your arm, bathed in a chemical soup and various cell promoters then injected into your arteries to combat neurones destroyed by Parkinson's disease? Within weeks, predict scientists, the new GE cells will lodge in the brain. Your ability to feed yourself, write letters, walk around and smile would return. Because the GE neurones are grown from your own tissue there would be no risk of rejection. And, faced with the alternative, you'd probably give it a go.
The human genome study, which involves the decoding of the millions of base pairs of DNA that make up the 23 human chromosomes, falls into the same category. This study goes back to the ground-breaking work on DNA carried out by Dr Crick and Dr Watson at Cambridge University in 1953 which was based on the discovery of a New Zealander, Dr Maurice Wilkins, while working at the University of London.
The possible spin-offs from the genome study at the Sanger Centre just outside Cambridge, are extraordinary. Once geneticists have written down the exact sequence of human DNA correctly, it will be there forever. Next step will be to establish which genes fulfil which function in the body.
"The entire collection of drugs on the market today act through 400 targets [biochemical sites within a cell]. Now, [using genomic technology] there are 70,000 to 80,000 available to work on ... By 2040 we should have typed everyone on the planet's genome," says the centre's Dr Peter Godfellow.
Despite the international fervour, little GE pharmaceutical work is being done in New Zealand - partly because of the anti-GE lobby, partly because of money.
Dr Bas Walker, chairman of the Environmental Risk Management Authority (Erma) the body responsible for assessing all living engineered organisms, says the authority has not had any applications recently "and probably won't until after the moratorium and Royal Commission."
Three field tests have made it through the regulatory system. The 200-strong PPL GE sheep flock, which is building up to sufficient numbers to produce enough milk for PPL to begin extracting the protein, which may help cystic fibrosis sufferers. New Zealand's involvement is solely at the milk production end of the work, while PPL 's new sterling 42 million plant in Scotland will carry out processing. Basically, says Walker who has a chemical engineering background, "it's manufacturing work."
Harry Griffin, of PPL's Roslin Institute, talks about how New Zealand was chosen for this work mainly because the country is free of scrapie. Keeping our relative cleanliness intact is important.
Next most important is AgResearch's programme, most of which revolves around genetically engineering milk in sheep and cattle to either produce medicines or modify the nutritional qualities of the milk. Two field trials have been cleared by Erma: the first involves adding extra copies of the cattle casein gene, so improving the protein content of milk; the second will inactivate the Beta-lactoglobulin Gene (BLG) reducing casein and making milk easier to tolerate for allergy sufferers.
AgResearch's other field trial involves cows which have had a copy of the human myelin basic protein (MBP) introduced, causing them to produce a protein in their milk which could help in the treatment of multiple sclerosis. Although MBP is known to have beneficial effects on the disease, it cannot yet be produced in sufficient quantities to be widely available. Earlier this month AgResearch's application was sent back by Erma for consultation with local Ruakura Maori. The project will be considered again next month.
Probably AgResearch's most controversial trial, which is also waiting for clearance from Erma, involves field-testing sheep genetically engineered by knocking out their myostatin gene. This gene, which is naturally inactivated in Belgian Blue cattle causing extra muscling - and confusion to anti-GE activist - regulates muscle development. AgResearch ultimately wants to study the role of the gene in heart attacks, muscle-wasting in old age and muscular dystrophy.
All other pharmaceutical work is still at the laboratory stage - some at Auckland University Medical School where molecular biologists are working on treatments for brain disease, stroke, epilepsy and cancer; work similar to that used to identify a predisposition to stomach cancer in a Maori family and the Malaghan Institute in Wellington has several medical trials under way involving imported transgenic mice. The University of Otago has five breeding pairs of imported transgenic mice to be used for research into cytoskeletal changes in oocytes and AgResearch at Ruakura has another set of GE mice for use in medical research.
Jim Watson's Genesis is working at the discovery end of genetic research by establishing a gene database for human skin. Its gleaming company headquarters in Parnell houses row on row of computers which, for the past six years have been spitting out the red, green, blue and yellow dots and squiggles that translate to DNA data. Work continues 24 hours a day: first shift starts at 7 am, the second ends at 11.30 pm.
"Basically we're building gene libraries from different plants, animals and trees. We don't have large industrial organisations in New Zealand funding basic gene research. It takes time, money and highly trained people," says Watson.
All GE salmon experiments, which were not for pharmaceutical use, have been suspended. Monsanto's application for field testing of GE wheat was withdrawn and despite Erma approval, Pioneer decided not to go ahead with its Bt maize field trials last spring.
Basically, the scientists have gone back to their labs.
At HortResearch in Mt Albert, one of the most recent projects is a 74-page report entitled, Genetic Engineering: The Public's Point of View. Inside the big rambling building it is very quiet, even for a lunch hour. Just a lone masters' student, a tray of test tubes in a worn old "shaker" designed to keep bacteria, used as a host for genetically engineered DNA, on the move. Equipment like this, which grows genetically engineered organisms which are then cloned in large numbers for experimental work, has been going on for decades.
Graham Le Gros of the Malaghan Institute, a charitable trust researching vaccines and cures for cancer, asthma and multiple sclerosis, is bloodied but unbowed. Over the past few months he has been targeted by the Green Party and the Animal Liberation Group outraged about work with GE mice that were supposed to glow in the dark.
"The mice weren't harmed in any way. They don't glow," says Le Gros. "They were just helping us find a cure for cancer."
Malaghan uses imported transgenic mice to track down how and where cells start misbehaving. "We try to work out precisely how a cell goes wrong so that we can construct the right kind of drugs. And at the moment the genes seem to be the best way of doing it."
But probably the worst worry for Le Gros is the escalating cost of research caused by New Zealand's super-rigorous regulatory system.
"It's increasingly difficult to do proactive, modern medical research in New Zealand," he says.
"Medical researchers are locked together with field-testing of crops. It's like comparing nuclear missiles with radiotherapy for cancer treatment."
Such testing is expensive in a user-pays world. Malaghan and other research institutes pay around $7000 for each mouse strain, mainly to get it through a committee made up of representatives from Maori, environment, scientific and lay groups. And says Le Gros, the full force of our regulatory framework hasn't kicked in yet.
As Dr Dan Cohen of HortResearch says, "the charges for applications are going up, probably to between $25,000 and $40,000."
However, Le Gros is confident that there are "some good people out there" who realise that New Zealand's economy is linked in with the rest of the world and that "without the basic tools we need for modern agriculture and biotechnology, New Zealand will die."
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