A Cloned Bull, or Just a Twin?

Despite arguments as to whether Gene is really a clone, it's clear that science has crossed another significant milestone.

ABS Global's Michael Bishop can be forgiven if he sounds a little harried after the events of last week - it's not every day that you get to talk to the world press about cloning a bull calf.

"We transferred the cells [for the calf] back in early 1996, around the same time as the Roslin Institute had created Dolly," explained Bishop, vice president of research for ABS Global Systems. "We were very close [in timing] with their experiments, but we're not in a race. Dolly was first, and she fueled a fire" surrounding cloning announcements.

That bull calf, Gene, is now famous for being the first bull created through a patented cloning process that some dispute as not actually cloning. ABS hopes the process will ensure full-term pregnancies for cloned cattle and provide the company with an unlimited supply of genetic material that can be used to make unlimited copies of a single species. The announcement comes at the same time that researchers at Japan's National Federation of Agricultural Cooperative Associations have reported developing a new cloning technology that could produce as many as 200 carbon copies of an animal from a single fertilized egg.

The problem with ABS's work on the nuclear transfers of fetal or adult cells has been that the placenta wasn't developed properly; pregnancies couldn't last beyond 55 days. "We eventually arrived at the idea of changing several proprietary procedures and doing a second nuclear transfer," Bishop said.

That process involves taking a cell from any tissue in a cow fetus, stabilizing it in a protein solution, and inserting it into an egg cell. That cell is then excited by an electrical charge that causes the pores of the egg and cell to open and allows their contents to fuse together. When cell division begins, every resulting cell will carry the same chromosomal information as the original fetal cell.

At this point, Bishop and his colleagues added a new step. They took a cell from the newly divided lot and fused it with a second egg cell, then allowed that to divide into an immature embryo, which was then implanted in the cow.

"What we have is a stable and permanent source of genetic material," Bishop explained.

And perhaps a new, more efficient way to develop clones of adult cows. Bishop said ABS is currently monitoring more than 10 pregnant cows carrying fetuses developed from fetal cells as well as from adult skin and kidney cells. Gene's survival rate was one out of 18 fetuses. Bishop says the chances are getting even better now.

"This telescopes the developments in cloning from three years to a month," said Lester Crawford, a doctor of veterinary medicine and director of the center for food and nutritional studies at Georgetown University. "You can get continuous improvement in a species. That's a whole new ball game."

Potentially, this development could accelerate adaptive radiation, the process through which a species over years develops heartier traits, chemically and physically, to survive. These developments will be quite useful in the area of tissue and organ production for the purposes of transfers and grafts, Crawford said.

Nonetheless, some in the biotech community dispute the use of the term "clone" with respect to Gene. "People have been doing this quite widely for over 10 years in sheep and in mice," said Allison Taunton-Rigby, chief of Aquila Pharmaceuticals. "This is nothing novel, except that it's happened in a cow. The next thing we'll see is a pig."

Taunton-Rigby's quibble is over the use of the term clone. She believes Gene is closer to being a twin than a clone because the cell used was from a 30-day-old fetus. By contrast, Dolly, the lamb produced by the Roslin Institute in Edinburgh, Scotland, was produced from the nuclear transfer of an adult sheep. That was more of a feat, she said.

"You had to worry about mutations [in the adult cell]. But with a fetal cell, you don't have any mutations," explained Taunton-Rigby, who attributed much of the excitement over Gene to the general media infatuation with cloning ever since Dolly came about. To wit, recent reports have recounted such developments as PPL Therapeutics producing the first transgenic sheep from an adult cell, and Friday Japanese researchers revealed a cloning technology that could produce as many as 200 carbon copies of cattle from a single fertilized cell.

For the weary Bishop, it has been a tough time. As happened with Dolly, news about Gene had been leaking out. Bishop concedes that he and his colleagues could no longer keep mum about Gene, even though they have yet to write a paper about their work and submit it to peer review.

"We picked this week because it was Gene's 6-month birthday, and he can enter the bull stud population," Bishop explained, trying to make the day seem like any other at the lab.