Advanced Cell Technologies (ACT), the company that announced the first human embryo clone and the first cloned gaur in 2001, last week helped to bring two bouncing bantengs into the world, only to euthanize one of them this week because it was grossly malformed.

While the first, still healthy, calf weighed a normal 20 kg at birth, the second was abnormally large at 36 kg. In vitro tinkering with cattle and sheep embryos can lead to such "large calf syndrome," which is commonly attributed to placental abnormalities, said Robert Lanza, vice president of Medical and Scientific Development for the biotech based in Worcester, Mass.

The normal calf suckled 5 liters of colostrum its first day, the second was reluctant, taking in only about 500 ml. "He had improved over the weekend, but nosedived," Lanza explained. The abnormal calf was euthanized on April 8. "With cows, almost all animals that make it past the first week go on to adulthood." The first calf is doing well, he said.

Two years ago, ACT's attempt to clone a gaur resulted in an apparently normal calf, dubbed Noah, which nonetheless died of dysentery two days after its birth in January 2001.

Still, Lanza said Noah provided a learning experience. ACT suspects the gaur's dysentery resulted from the colostrum they pumped directly into the calf's stomach, since he wouldn't suckle. With the bantengs, the company consulted endangered species birthing experts at the San Diego Zoo, who explained that wild ox calves could not be nursed unless they were convinced they were safe, Lanza said.

ACT cloned the embryos using frozen skin cells from a male banteng (Bos javanicus) that died at the San Diego Zoo in 1980. Banteng nuclei were inserted into enucleated cow eggs, and ACT collaborator Trans Ova Genetics of Sioux Center, Iowa, transferred embryos to 30 Angus cows. Of 16 pregnancies, two yielded live births. Both banteng clones were born via Caesarean section seven–to–10 days before term; the first on April 1, the second on April 3.

Given the nuclei are from one species and the egg and its mitochondria are from another, such cross-species cloning is risky, said Lanza. "We're in uncharted territory here. You'll need to look at each pair of species on an individual basis. In future, you might be able to correlate certain markers with certain viability, but until you implant the embryos, you can't tell," he explained. "That's going to be slow in coming. In the meantime, you have species that are dying off and you need something now."

Rudolf Jaenisch of the Whitehead Institute in Cambridge, Mass., said it remains to be seen whether the apparently normal banteng calf goes on to develop problems, citing clones that developed malformed brains, immune defects, kidney and lung problems and tumors after birth.

"Dolly was obese and had arthritis," Jaenisch said. "All cloned mice die early. You expect this of cloned animals."

Such risks are among the reasons why Jaenisch and others say it would be dangerous and irresponsible to attempt human cloning, which reproductive scientist Panayiotis Zavos claimed this week to have done.

Zavos' report of a four-day-old eight–to–10 cell embryo, which he called the first human cloned embryo created expressly for reproductive purposes, is described in a report appearing in the June 2003 issue of Reproductive BioMedicine Online.