AgResearch is bidding to create herds of genetically modified animals to help people fight rare conditions. Chris Barton reports on both sides of the vigorous debate
John Forman begins his presentation at the NZBio conference with photos of his twins, Timothy and Hollie.
The pictures are a blunt reminder of why he's advocating more research using transgenic animals.
Not that his twins, now 35, who suffer from the rare genetic disorder Alpha-mannosidosis, would be likely to get any benefit.
"It's about trying to make sure that families in the future who are affected by these diseases have better options, better outcomes and more therapies available to them," says Forman, who is executive director of the New Zealand Organisation for Rare Disorders.
"If by chance the enzyme that is being trialled for the condition Tim and Hollie have might have benefits for some aspects of the disease in adults, then that will be a bit of a bonus. But we're not really hanging out or expecting major impacts from that."
Forman is talking about promising new developments in enzyme replacement therapy, not only for the disease affecting Timothy and Hollie, but also other lysosomal storage diseases such as such as Gaucher, Fabry and Pompe disease - diseases which are progressive and degenerative, often fatal at an early age and which bring substantial physical and mental deterioration.
The therapy works by intravenously giving the patient the enzyme their body lacks so it enters the bloodstream, is internalised by the body's cells and then used by the lysosome, the cell's recycling centre.
The replacement enzymes are currently made by genetic modification of Chinese hamster ovary (CHO) cells, but may one day come from the milk of carefully modified New Zealand cows, which is why Forman has made a submission in support of AgResearch's application in March to develop genetically modified goats, sheep and cows to produce human therapeutic proteins.
The application, heard by the Environmental Risk Management Authority (Erma) is opposed by anti-genetic modification groups including GE Free New Zealand which, in June 2009, stopped a similar AgResearch application in the High Court.
But last month the Court of Appeal lifted the ban, allowing AgResearch to proceed with its original application.
The argument has been largely procedural - whether the broad and generic nature of AgResearch's application fits within the scope of the Hazardous Substances and New Organisms Act. The battle may not yet be over, with GE Free NZ now considering taking the matter to the Supreme Court.
Ongoing delays like this are particularly frustrating to Forman and others who know first-hand the substantial burden such diseases put on both patient and their family.
"Timothy and Hollie are quite significantly disabled. In those lysosomal diseases where treatments have been developed, the outcomes can be significantly different - a much better quality of life and major amelioration of many of the symptoms," he says.
"When the critics say there are issues about safety, there is no one who is more interested in the safety of this than the patients and the families of the people who would be treated with these medicines."
Though current enzyme replacement therapies are produced from genetically modified cell lines "fermented" in bioreactors in much the same way as synthetic insulin is produced, Forman says there are a number of advantages to using mammals' milk to produce the proteins or enzymes.
Using a mammalian system, he says, enables better uptake of the proteins by the patient's cells, and minimises the chances of rejection by the patient's immune system.
Producing milk from a transgenic herd also avoids the complex, expensive laboratory and industrial-scale production processes that ferment genetically modified animal cell lines.
It also avoids the sort problems Genzyme, the world's largest supplier of recombinant human therapeutics, had in 2009 when its CHO cell fermentation plant had to be shut down and sanitised because of viral contamination in a bioreactor.
With milking transgenic animals there is reliability of supply plus the possibility of a valuable export business.
"You have animals which are extremely precious and would have the most cosseted and pampered life. They would be extremely valuable.
"A cow with the right kind of protein in its milk could be worth millions of dollars," says Forman.
Known as biopharming, the process is already producing results for companies like GTC Biotherapeutics. In 2009, the company received United States Food and Drug Administration approval for a human anticlotting protein produced by a herd of 200 bioengineered goats living under carefully controlled conditions on a farm in central Massachusetts.
The transgenic herd originally hailed from New Zealand.
But though the therapies Forman and others advocate clearly have benefits, they also raise the spectre of possible unknown effects of genetic modification.
"I have no problem whatsoever with new medicines provided the entire production line is subjected to open and transparent assessment," says Professor Jack Heinemann of Canterbury University's School of Biological Sciences.
"We can tolerate any technology provided we are fully and honestly informed and society as a whole judges the benefits of that technology exceeding potential harms."
Heinemann, who has been described as both a "card-carrying gene-jockey" and "the country's senior critic of gene-tampering" researches in the field of genetic engineering.
He says it's important to recognise genetic modification for what it is: "When you mess with the DNA that codes genes, you change its structure and its sequence - genes are informational. It's not just the chemistry of the DNA."
He doesn't like language that seeks to minimise or alter perceptions of what happens with genetic modification. Heinemann is particularly critical of the terms "cisgenics" and "intragenics" (genes from the same species or genome) used instead of "transgenics" (genes from different species) for describing some GM products.
The terms had an outing last month in a Royal Society paper, Genetically Modified Forages: Emerging Issues which stated: "The implications of cisgenics and transgenics are sometimes viewed differently amongst scientists, regulators, and the general public. Cisgenic transformation may appear to conform more to the 'natural order' of species isolation and therefore may be more acceptable for that reason to the New Zealand public."
Heinemann says sourcing the gene from the same species doesn't change the fact that with genetic modification, genetic material (DNA) is taken out of an organism, put into a test tube - "a completely human-designed environment" - and then put back into the organism through a process that is alien to the normal maintenance of the material.
The newly sequenced gene snippet makes the new organism "as different as if it came from any other species on earth" - novel and unique enough to be granted a patent.
Heinemann says it's farcical to say that species identity is preserved through the GM process. Or that just because a modified gene sequence is modelled on a gene from the same species that it is somehow automatically less harmful.
"Whether you use the word cisgenic or transgenic, it doesn't matter. It's changing the order of nucleotides in an existing genome that has historically been under physiological control and which we have millennia of interactions with."
Heinemann says the problems in assessing risk arise when the product of GM becomes the focus.
"When what you make by genetic engineering has to be the product you sell, that's when the conflict arises."
He advocates for independent assessment of the science to support safety - easier said than done in an environment where the developers of GM products are also tasked with the responsibility of assessing risk.
"We need scientists independent of these commercial imperatives," says Heinemann. "And we need appropriate levels of private or public funding to do that." He says it's also necessary to eliminate commercial proprietary secrecy around GM products and especially GM crops, where patents and confidentiality agreements prevent scientists from testing for unknown effects.
What worries him more is that much of the GM safety testing done by independent scientists to date - especially for GM crops - has happened after the GM product has been introduced to the environment.
And only now is there mounting evidence of unintended effects - such as herbicide-resistant weeds and insecticide-tolerant insects. It's also only in the past few years that the use of GM crops such as soybeans and corn has increased to the point that today about 10 per cent of arable land worldwide is used by GM crops.
As Heinemann points out, because the Western diet has so many elements of processed food and so many of those elements come from corn or soybeans, our diet almost certainly now includes some level of genetically modified corn or soybeans.
"It is a low-level contamination across our food supply, but the total amount we ingest is probably negligible," says Heinemann.
Whether we like it or not, GM products are, at some level, in our food. The problem is we have no way of knowing what effect that might have.
"Testing for an unknown effect that comes through food takes an enormously concentrated and dedicated surveillance system. We don't have that - nobody does."
The situation has led some like Dr Nina Federoff, the science adviser to the US Secretary of State to advocate for more GM - the argument being that since GM products are in our food anyway without causing any obvious problems, we can safely have more. GM by complacency.
It's this sort of faulty argument that Heinemann says regulators and others need to be vigilant about. Yes, it's correct that both New Zealanders and Americans have not escaped eating GM food he says.
"But the implication that there will be no harm from eating this food at higher doses and for longer times because there has not been a health harm detected in a few years at current doses, is not scientific."
