Treading warily in GM minefield

By SIMON COLLINS

Cows have been shaped by human intervention. They were bred over 8000 years from a wild ox which stood almost twice as tall as its modern descendant but produced far less milk.

We have created an animal that is a living milk factory, yielding many times the amount of milk that its ancestors did. Our cows have been sired by only a few prize bulls, their semen collected and inserted by human hands.

Yet when AgResearch decided a few years ago to fine-tune this milk machine to produce milk laced with human proteins that might help people with diseases such as multiple sclerosis, it drew 850 objections and a costly High Court battle.

When the Bioethics Council ran focus groups to test the idea of putting human genes into other animals for a report issued in January, it found "almost universal rejection".

"Some find the idea so repulsive that they cannot contemplate or fully discuss it," the report said.

"Others find the idea so foreign that they cannot imagine why anyone would think of such an idea, unless they had 'a sick mind'."

The report seemed to draw up battle lines between the Government-appointed council, chaired at the time by former Governor-General Sir Paul Reeves, and the biotechnology industry which the same Government had designated one of the country's three top priorities for economic growth.

But last week, after eight months of "dialogue" with the public, the council finally produced another report - the first setting out the council's own views on any subject.

Its own views turned out to be much more favourable towards putting human genes into other organisms than its early view of public "repulsion" had suggested.

So what changed its mind? And has it come up with an ethical path that can guide us forward?

Former Labour MP Jill White, who now chairs the council, says people in the dialogue meetings were prepared to put human genes into other organisms when they could see it would relieve human suffering.

"The dialogue process was very deliberately set up as a dialogue, not a debate, with skilled facilitators.

"This gave the opportunity for people to share their views and listen to others' views," she said.

"The idea of the dialogue was that it enhanced understanding even if there was not agreement. The dialogue process was very successful."

At present, there are broadly two reasons why scientists put human genes in other organisms.

One is to make "bioreactors", such as AgResearch's cows.

The other is to test new drugs or other treatments on animals before trying them on humans.

There is, of course, nothing new about extracting medicinal substances from plants and animals.

But the idea of injecting new genes to make the plants and animals produce particular medicinal substances is still relatively novel, even in the United States where modern genetic modification (GM) began.

Genetically modified bacteria are used to produce human insulin, human growth hormone and interferon, a substance in human bodies which strengthens resistance against hepatitis and certain cancers.

Speakers at the recent Bio 2004 conference in San Francisco outlined other projects to genetically modify goats, hens, corn, tobacco and safflower to make them produce medicines in their milk, eggs, plants and seeds.

But they said investors were holding back from funding more such projects because of the consumer backlash against GM products, especially in Europe.

Genetic modification of animals to give them human diseases in order to test new drugs, or simply to study how the disease develops, is also new - but increasing fast. In New Zealand, the number of genetically modified animals notified to ethics committees quadrupled last year to 6711.

Of these, 6555 were mice that underwent "little suffering", 52 were mice with "no suffering" and 104 were cattle, which also experienced "no suffering".

Under the Animal Welfare Act, all "manipulation" of animals either as bioreactors or in research requires approval by an animal ethics committee. Approval can be given only if the likely benefits "are not outweighed by the likely harm to the animals".

THE Bioethics Council treads carefully through this minefield by noting first that most genes found in humans are the same as, or similar to, genes found in many other animals. But it says genes "are more than chemicals. They also have cultural significance".

Genes are seen as part of our "lineage, blood, whakapapa or creation". Eating substances containing human genes is culturally "inappropriate".

So the council endorses the GM Royal Commission's view that "wherever possible, non-food animals [should] be used as bioreactors rather than animals that are a common source of food".

Equally, "wherever possible, synthetic genes or mammalian homologues [equivalents] of human genes [should be] used in transgenic animals to avoid the use of genes derived directly from humans".

That does not quite rule out AgResearch's cows, because the institute can argue that bioreactors need to be animals that produce large amounts of milk in which a human protein can be expressed.

As health researcher Dr Martin Kennedy puts it: "You could do it in mice, but you'd get such a tiny amount of milk. The transgenic cow will produce enough protein to treat perhaps 1000 humans." But the proposal does erect a hurdle for bodies like AgResearch to cross if they want to modify animals in the human food chain. They will have to either make the genes synthetically in the laboratory or show that there is no feasible, or "possible", alternative to using a human gene.

Next, the council proposes a complete ban on modifications that would make animals "speak, think or look like us", because "these changes might well (and perhaps should) affect the moral status we ascribe to these modified non-human organisms".

This is merely a pre-emptive strike, because no one anywhere in the world has actually made an animal do these things yet.

The council also recommends that the Animal Welfare Act be changed to require ethics committee approval of any modification of an embryo or foetus that might cause suffering later in the animal's life.

That would close what animal rights advocate Deidre Bourke calls "a massive gap" in the current definition that counts an animal's life as starting only in the second half of pregnancy.

But having imposed these conditions, the council concludes that there is no ethical reason to stop putting human genes into other organisms where these conditions are met.

"The use of a human gene for the production of a single protein in the host organism does not raise sufficient cultural, ethical or spiritual reasons in itself to prevent this kind of use in plants and animals," it says.

Its dialogue with the public found "wide acceptance of the use of human genes in other organisms for the relief of human suffering".

But people were also concerned about the suffering of animals. "Even those who accepted some use of animals in research felt there needs to be a balance between the potential benefits of the research and the burden of suffering of the animals."

Amen, says Kennedy. "Most of it is kind of commonsense," he says.

Bourke says animal rights advocates also accept the need to balance human benefits against the costs to animals. But she says that balancing process should be done by public representatives whose decisions should be public.

Medical ethics committees, which approve research on humans, hold meetings that are open to the press and public.

But animal ethics committees meet in secret, do not publish their agendas or decisions, and even membership is secret as a protection from animal rights activists.

Bourke says that at least they should have to publish summaries of their decisions, explaining how they weighed up the costs and benefits.

"There is a cost-benefit calculation being made, but it's being made by the scientific community, which biases it."

Bioethics Council:

Jill White, former Labour MP, chair

Dr Helen Bichan, former mental health manager

Dr Chris Cunningham, Maori health lecturer

Eamon Daly, doing PhD on computer ethics

Anne Dickinson, Catholic Bishops Conference

Professor Hirini Mead, Ngati Awa kaumatua

Waiora Port, doing PhD on DNA testing for Maori

Graham Robertson, farmer

Piri Sciascia, Victoria University pro-vice-chancellor

Professor Ian Shirley, social policy professor

Dr Martin Wilkinson, community health lecturer .