SCIENCE: July 05, AU Edition

COPY CATS
Entrepreneurial American scientists are destined for the dog house, says Susanne Quick
It’s just another brown brick building in a suburban American business park. But Suite J at the Waunakee Business Center in Wisconsin is about to turn into the animal cloning debate’s ground zero. Genetic Savings & Clone Inc. – the entrepreneurial outfit that introduced the first cloned pet cat to the world in December – is opening its doors in this small Madison, Wis., suburb this month. The company’s CEO, Lou Hawthorne, has promised that by year’s end, a dog will be born here.
In the eight years since Dolly the Sheep’s birth was announced to the world, research into animal cloning has progressed in ways few dreamed possible a decade ago.
Scientists have now cloned barnyard animals and endangered species. They’ve created cloned cows from frozen steaks and cloned mice from cancer cells. They’ve talked about resurrecting extinct creatures such as woolly mammoths and Tasmanian tigers. And with the news on Thursday that soft tissue from dinosaurs had been discovered, re-creating these giant lizards does not seem so farfetched. Despite the scientific excitement, creativity and ingenuity that have inspired and driven this research, cloning remains uncomfortable – even freakish – for many people.
Who and what are the clones? Are they healthy animals or deformed monsters? How many animals are sacrificed in the pursuit of one healthy clone? And, in the end, what will it lead to?
As ethicists and scientists weigh the motivations for animal cloning – improving the food supply, fighting disease, saving endangered animals – the arguments for and against cloning mutate and evolve along with the research advances.

That debate is now moving to the backyard.
In December, Genetic Savings & Clone announced the birth of Little Nicky, the first cloned cat to be sold as a pet. The recipient, a Texas woman known only as Julie, paid $50,000 to have her beloved – but dead – kitty cloned. While some say she was swindled, Hawthorne believes she was given an incredible, if expensive, gift.
‘Our product is based on love’, Hawthorne said.
David Magnus, director of Stanford University’s Center for Biomedical Ethics, scoffed at this claim. He said the high death rates and possible cruelty that go into cloning make Genetic Savings & Clone’s product anything but ‘loving’.
Also, he and other critics said consumers are being duped: The animals they think they are getting – their original pets – cannot be reproduced.
And finally, they think Genetic Savings & Clone’s product is grossly frivolous in light of the number of animals in shelters who need homes.
‘Everything about this is objectionable’, Magnus said.
But Autumn Fiester, a bioethicist at the University of Pennsylvania, said there isn’t evidence to show that animals are suffering – at least any more than commercially bred dogs or cats.
She added that the claim that pet owners are being duped is condescending. As for the frivolous argument, she says, ‘Then you’re arguing against buying any luxury good.’ Among those involved in cloning, she is in the minority.
Robert Lanza, vice president of medical and scientific development at Advanced Cell Technology – a Worcester, Mass., company at the forefront of cloning technology – called it ‘troubling.’
Rudolf Jaenisch, a professor of biology at the Massachusetts Institute of Technology and a researcher at the Whitehead Institute for Biomedical Research, called pet cloning ‘ridiculous’ and ‘preposterous.’
Somatic cell nuclear transfer – the shop name for cloning – is conceptually a pretty easy process.
A cell – such as a skin cell – is taken from an adult animal. The nucleus, and the DNA it houses, is sucked out and placed next to an empty egg cell that’s had its nucleus removed. The new egg-nucleus combo is then jolted with electricity or bathed in a chemical cocktail.
‘What you want to do is basically trick the egg into thinking it’s been fertilized by a sperm’, said Neal First, a retired professor of animal sciences at the University of Wisconsin-Madison, and the first researcher to clone cattle.
If all goes well, the duped egg starts to divide, eventually creating an incipient embryo, which researchers implant into a surrogate animal.
While this may sound pretty straightforward, it’s actually a messy, hit-or-miss process that yields few successful clones.
Depending on whom you talk to, the number of successful clones – i.e., those which survive beyond birth – can run as low as one-in-1,000 to as many as 15 percent.
Researchers believe this is the result of a host of molecular issues, some they can pinpoint, others they can’t.
The mystery is in the egg. ‘There are molecules in the egg that allow the DNA to reprogram’ and start anew so that it’s read as the blueprint for an embryo, not an old skin cell, Lanza said.
But what those molecules are and how they work remains elusive.
There is also an issue of extra DNA in the egg. Even though the egg’s nuclear DNA is removed, other genetic material remains floating around the egg cell in a form known as mitochondrial DNA.
No one knows for sure what effects this might have on a developing clone embryo, but it does mean that the clone, despite its name, is not an exact genetic duplicate of the donor. It has some other DNA that may or may not affect its development.
Then there’s the issue of imprinting. Mammals carry two copies of each gene: one set from their mother, the other from their father. But only one of these copies is active at any one time.
In a clone, ‘the normal battle between mom and dad’ is not taking place, Lanza said. The end result: critical messages from the genes are being lost during an embryo’s development, potentially leading to cardiac problems, respiratory ailments and ‘a messed up placenta.’
The hurdles don’t end here.
When DNA is in a quiescent state, it looks like spaghetti noodles with proteins attached to it. This means that when the skin cell DNA is sucked out, it’s carrying a lot of protein baggage. It is possible these proteins may get in the way of the egg-skin cell DNA fusion.
Researchers at Genetic Savings & Clone say they have solved this problem by using a new technique called chromatin transfer that cleans the DNA. The result, according to Hawthorne, is higher efficiency.
‘Our losses are well under 50 percent’, he said, adding that such losses are typical in commercial breeding.
Magnus and others question these claims; scientists at Genetic Savings & Clone have not published their results. But Jim Robl, president of a South Dakota biotech company called Hematech and one of the developers of chromatin transfer, said he, too, had gotten good results using this method to clone cows.
Yet, the battle over pet clones only partially hinges on technical and molecular hurdles.
These animals are behaviorally complex. They are not just products of a strict genetic blueprint, but of the multicolored and textured tapestry of their environment and experiences.
This means that a consumer who’s paying thousands of dollars in hopes of getting the same dog or cat will be getting an animal that behaves differently than the original. That, said Magnus, is ‘a rip-off.’
Finally, critics of pet cloning said there’s the issue of the millions of animals who don’t have homes that are living on the streets or housed in shelters.
Magnus and Spiegel-Miller believe Hawthorne’s business is minimizing the plight of these animals.
They charge that the money Hawthorne’s clients are willing to spend on a clone would be better used on these other animals, that Genetic Savings & Clone clients should head to a local shelter, pay $50 for a cat or dog that needs a home and donate the rest to the shelter.
That would be a more ethical way to spend their money, they say.
Fiester and Hawthorne dismiss the criticism as baseless.
‘Why should someone who loves their cat be more obligated
to donate money or help shelter animals than someone else?’ Fiester said.
He also threw back the notion that cloning for agricultural or medical purposes is somehow more ethical.
In the end, he said, the future of the pet cloning business will depend upon the quality of the product.
If Genetic Savings & Clone can create animals that pet owners are happy with – animals that aren’t sick or compromised and behave in ways similar to the original – the business will succeed, Hawthorne said.
His scientists also are looking into how to enhance pets and make them live longer and healthier.
‘Our clones will be better than normal,’ he said. ‘Clones are going to become the preferred pets.’