Cloning raises morality questions

By SIMON COLLINS

AgResearch is proud of Elizabeth, its prized friesian dairy cow whose genes were implanted four years ago into a litter of 10 apparently healthy calves.

Dr Paul Atkinson, AgResearch general manager of science, has shown Elizabeth's photo at several conferences and will be showing her off again at the Pacific Rim Biotechnology Conference in Auckland next week.

Elizabeth's fame is deserved - producing 10 genetically identical cloned calves is quite an achievement.

On average, AgResearch says, only 6 per cent of the cloned embryos it creates survive to become 3-month-old animals ready to wean.

If Elizabeth's brood was typical, that means about 157 other embryos were created and lost to produce those 10 healthy calves.

Most of the rest aborted spontaneously during pregnancy. Scientists aborted others deliberately because they were growing abnormally large or showed other obvious deformities.

Since the photo at top right was taken, three of Elizabeth's 10 clones have died: one at six months with skeletal problems, and two that had to be killed because of other ailments.

The other seven are still alive on AgResearch farms. Most have produced calves, and some have now calved twice.

"The offspring of the clones are entirely normal," Atkinson says.

Dr Nick Agar, a Victoria University philosopher who has just published a book in Britain on the ethics of cloning, believes New Zealanders must balance the cost of those offspring against the clones that died.

"If you look at the reports of the cloning of mammals, there is a huge quantity of suffering out there. It's far from a secure, perfected science."

Dr Ian Wilmut, the Scottish scientist who created the first cloned sheep, Dolly, in 1996, published a study last April highlighting clones that had been born with placentas up to four times the normal size, and others that became grotesquely fat, developed lung problems or had malfunctioning immune systems.

"The widespread problems associated with clones have led to questions as to whether any clone is entirely normal," he said.

Rudolf Jaenisch, a Massachussetts Institute of Technology scientist who will visit New Zealand in January, published a study in September showing that cloned mice had so many genetic abnormalities that you could tell a clone just by looking at its genes.

Yet Agar, 39, believes we should keep an open mind on whether cloning will always be defective, or whether these are just "teething problems".

"I'm more of a technology optimist than a technology pessimist."

Like Agar, the Government is looking for a clear ethical path.

The director of animal welfare, David Bayvel, says cloning is being reviewed by the national advisory committees on animal ethics and animal welfare.

"Both are liaising with their counterpart committees internationally.

"New Zealand's consideration of this is not unique. There are similar discussions in Europe and North America."

He adds: "My best guess is that we'll probably publish something in the middle of next year."

Parliament has already banned any attempt to clone humans without specific approval of the Health Minister after public consultation.

But at present, animal cloning is not subject to the rigorous process of public hearings that scientists must go through to genetically modify plants or animals because cloned animals are not genetically modified.

AgResearch has been free to keep its cloned calves anywhere on its farms, rather than in the double-fenced "containment area" where GM animals must be held.

It has also been free to sell cloned animals. Several cows are already pregnant with cloned embryos based on cells from the top bulls of artificial breeding company Ambreed, which hopes to sell any successful clones to China.

The only constraint on animal cloning is oversight by local animal ethics committees - in AgResearch's case the Ruakura committee, which checks on all the Crown research institutes at Ruakura, near Hamilton.

By law, the committee must include one representative each from local government, the Veterinary Association and the SPCA, as well as people from the institutions being checked on.

But SPCA national chief executive Peter Blonkamp says his organisation's nominee cannot be named and has not reported to the national body about cloning.

"Quite frankly, at this stage we don't know enough [to comment]," he says. "We are waiting for far more detailed reports on this."

As AgResearch practises it, cloning involves extracting cells from the uterus of a donor cow such as Elizabeth and injecting them into the unfertilised eggs of dead cows - obtained from the local abattoir - which have had their genetic material removed.

The two cells are fused together using a tiny electrical pulse. The reconstructed cell is then activated using another electrical pulse or chemical signals, and is "fed" by hand in a petri dish for a week until it has grown into an embryo of about 150 cells.

The embryo is then placed in the uterus of a surrogate mother.

In just six years since the birth of Dolly, cloning has mushroomed in research institutes and companies around the world.

Italian doctor Severino Antinori claimed on April 7 that a woman was already eight weeks pregnant with a cloned embryo. If his claim was true and the foetus has survived, the first cloned human baby should be due to be born about now.

Agar has already tried to map a way to think about the technology in Life's Intrinsic Value, published by Columbia University Press last year.

"I was expressing the idea that everything that is alive has some intrinsic value," he says.

So Agar is against the view that a cow such as Elizabeth can be experimented on at will because she is "just a thing".

But he believes it is also too simplistic to ban all experiments on animals just because the animals have value in themselves.

"You know that attacking Iraq will kill a lot of innocent people, yet lots of people will think it's still worth doing.

"A cow is a morally valuable thing and I should be worried about how to treat it, but it's not straightforwardly the case that I can't do anything because it's morally valuable. It just means you have to take it into account."

In his new book, he proposes what he calls a "welfare test" that would have to be met to justify human cloning: "Is the person about to be brought into existence likely to lead a life that is worse than no life at all? If yes, then we have a moral duty not to bring them into existence."

In other words, if there is a high chance that the clone will be horribly deformed and have a miserable life, then it would be better not to create it.

However, he notes that modern cloning does not necessarily involve creating a whole new person.

Instead, the technique called "therapeutic cloning" tries to grow undifferentiated cells into replacements for specific damaged body parts such as nerve cells, heart tissue or insulin-producing cells.

"I think the moral objections to therapeutic cloning are bad ones," Agar says.

"But in order to get therapeutic cloning to work, experimenters are going to have to be empowered to cause quite a bit more suffering and do quite a bit more practising on animals before you try it on humans."

Green Party co-leader Jeanette Fitzsimons disagrees. She cites Jaenisch's and Wilmut's studies as evidence that cloning is so likely to produce genetic defects that it should be banned completely.

In January, the company based on Wilmut's technology, PPL Therapeutics, announced that Dolly had arthritis.

Some scientists believe that animals cloned from adults start life genetically older than they seem, and will age more quickly.

Although AgResearch may point to possible long-term medical breakthroughs, Fitzsimons alleges that its actual reason for cloning Ambreed's prize bulls is simply to make money.

"They have been carried away by the idea of a perfect copy.

"Clearly, cloning will never give you a perfect copy. There is a question of whether it can give you a normal animal, because the genes will grow in distorted ways."

But Atkinson and AgResearch cloning expert David Wells say this is not true. They insist that clones such as Elizabeth's calves are genetically identical in the same way as identical twins.

Yet just as identical twins are never exactly the same, so there are variations in the way the genes are expressed in different clones.

"If you look closely at that photo of Elizabeth, you will see that the colouring on the animals is not identical," Atkinson says.

These minor differences are "epigenetic", meaning they will not be passed on to the clones' offspring.

"The key thing to realise is what is being produced," says Wells.

"The animals are there to provide semen for future breeding, and the important point is, what is the health of the offspring of the clones from sexual reproduction.

"All the work we and others have done around the world strongly shows that, whilst there may be issues with the health of clones and the losses postnatally that we talked about, the offspring from the clones appear normal."

Wells concedes, however, that it is too soon to be sure. AgResearch has created about 100 clones, of which about 35 have produced offspring.

"We need to monitor those animals for a long time.

"Mice might have a lifespan of two years, but the biological limit is about 20 years in livestock species.

"It's early days."

* Nicholas Agar's Perfect Copy: Unravelling the Cloning Debate will be published next month by Icon Books (price $29.95).

Further reading
Feature: Cloning

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