HOW MUCH FOR THAT CLONE IN THE WINDOW?

A number of factors determine the cost of cloning. Pet owners don't usually want more than one copy of a beloved animal, but the relatively high failure rate of cloning requires that many embryos are created and implanted in surrogates. Cow cloning efficiencies average around 30%, according to Jim Robl, president and chief scientific officer of Westport, Conn.-based Hematech, which has laboratories in Sioux Falls, SD. About 1% to 6% of transferred swine embryos and about 5% to 10% of cloned sheep embryos result in offspring, but many of those "are not exactly healthy animals," says Jorge Piedrahita, of the North Carolina State College of Veterinary Medicine in Raleigh. Goats have a cloning efficiency of 3% to 7%, and tend to have fewer abnormalities than sheep. Not enough data exists to determine the cloning efficiency of cats, though the first cloned cat reportedly took 87 embryos to produce a kitten, a cloning efficiency of roughly 1 percent. The company declines to say how many attempts it took to create Little Nicky.

<p>CLONING BY CHROMATIN TRANSFER:</p> © 2004 Society for the Study of Reproduction, Inc. 1. Cells permeabilized with Streptolysin O (SLO) 2. Mitotic extract containing an ATP-generating system promotes chromatin condensation and removal of nuclear components (arrows). 3. Cells resealed with CaCl2. 4. Resealed cells fused to enucleated oocyte. 5. Oocyte activated to elicit pronuclear formation.

Quality control is another issue. Clones can have genetic flaws, be oversized, or just look different from their genetic donors. "Every single clone has to be perfect," says Genetic Savings and Clone CEO Lou Hawthorne. "The public won't put up with a large number of losses."

Genetic Savings and Clone now has several hundred clients who have banked pets' genetic material, and they have garnered about 10 new ones each day since the Little Nicky announcement, says Hawthorne. He estimates the client list would jump into the thousands if the price drops to $20,000 per clone, but too many clients could also overwhelm production capacity. That situation will change in February when the company rolls out a new facility outside of Madison, Wis. In 2005, the company hopes to clone about 40 cats and three or four dogs. Dogs remain a challenge because their complex reproductive systems are poorly understood.

One way companies may be able to lower the price is through sharing resources with related divisions of a larger company. Via-Gen, a 35-employee company that began life three years ago as a spinoff of Genetic Savings and Clone, is one of three components of a larger company called Exeter Life Sciences. The others are Arcadia, an agricultural biotech company, and Kronos Optimal Health, both headquartered in Phoenix, Ariz. The three divisions share corporate functions, and "certain scientific synergies," says Davis.

ViaGen harnesses cloning technology to perform genetic selection on shrimp, specifically trying to produce aquaculture species with resistance to viral disease, "which is about $1 billion a year loss to the industry," says Davis. Such "turbo-charged" selection is a major part of the business model for ViaGen, which recently signed a $5 million deal with Premium Gold Angus Beef for DNA identification of cattle, using Affymetrix technology, "to let customers know they're buying what they say they are."

<p>Cloning Companies</p>

Simon Brodie, CEO of Los Angeles-based Geneticas, another company that has entered the market, says his company plans to announce in July that they have brought the cost of cloning a cat to below $10,000. However, the company has yet to produce a clone, and some doubt such prices are realistic. "I don't think it's going to come down to the day when you can get a clone for $5,000," says Piedrahita. Hawthorne agrees. "There are companies out there promoting lower price points," he says, "but they're just blowing air. They have no staff, no intellectual property." He says his company has an exclusive license to use chromatin-transfer technology in cats.

In chromatin transfer, donor cells are treated with streptolysin to make their membranes more permeable, and mitotic factors to make the chromatin more accessible to oocyte factors. A study in calves suggests that gene-expression profiles characteristic of early embryonic development are more likely to show up in chromatin transfer-derived embryos than nuclear transfer-derived embryos (the older method used to clone Dolly the sheep), though the two methods have not yet been compared in a head-to-head trial with sufficient power to determine a significant difference.

Scientists at Hematech developed chromatin-transfer technology, and then spun off Aurox about five years ago, says Aurox CEO James Barton. Aurox has licensed the use of the technology to a number of companies in addition to Genetic Savings and Clone, which holds the exclusive right to use the technology in cats and a research license for its use in dogs. "All of our licensees enter into the same agreement, whereby if they make improvements in the technology they transfer those improvements to Aurox, and every other licensee has access to those improvements," says Barton. "We're hoping that as more people use the chromatin-transfer technology, that everyone will be able to share in the improvements."