Dolly does battle with the wolves

Biotechnology firms face a long struggle to win over the critics of cloning. Dane Hamilton reports

When President Clinton picked a cloned sheep named Dolly to raise "serious ethical questions" about human replication, Ron James wasn't surprised.

Mr James, managing director of PPL Therapeutics, the company that created Dolly, expected that kind of response, although not necessarily from the leader of the free world.

"Not since the splitting of the atom has a president ever got involved in this kind of issue," said Mr James, founder of the Scottish biotechnology company that created the animal in collaboration with the Roslin Institute, a non-profit agriculture research centre.

Scientific advances like PPL's creation of Dolly, the world's first sheep cloned from an adult cell, are often misinterpreted, he explained.Human cloning, he added, is still not feasible, although some experts disagree.

"If some rich tycoon came to me and wanted to be cloned, we would know how to start and what to do, but we couldn't do it," said Mr James.

In an office surrounded by a 3,000-sheep farm in the rolling hills outside Edinburgh, the venture capitalist-turned-entrepreneur said he expected a swift response after Dolly made her world debut.

He said his and other biotechnology companies still have a long struggle to persuade investors and the public about the real value of Dolly for both agriculture and human health.

One objective is to create an animal which generates proteins that people with genetic diseases lack. New emphysema treatments and lucrative nutritional supplements may also emerge from the research. Yet issues such as the plausibility of human cloning and even the timing of the announcement overshadowed the news.

"It irks me," said Mr James. "People accused us of keeping this a secret for seven months!"

The decision to let Dolly reach adulthood before telling the world was perhaps emblematic of the methodical way in which the company has refined the technology over the past nine years, a process it now plans to apply to cows.

It had to ensure the animal was a genuine clone - a genetic duplicate of its parent - which tests would show. Next, the discovery had to appear first in Nature, or a science magazine of similar stature, to give it credibility. However, several days before the Nature publication date, a Sunday newspaper broke the magazine's embargo, unleashing a torrent of media attention and a swift response from Mr Clinton.

Announcing his ban on federal money being used for research into human cloning, Mr Clinton said humanity must "resist the temptation to replicate ourselves".

"Right from the beginning we made it very clear we have no intention of cloning humans," said Mr James.

Dolly, named after Dolly Parton because the cells that made the animal came from breast cells of Dolly's "mother", is just part of a scientific process led by PPL and rival biotechnology companies, Pharming BV and Genzyme Transgenics Corp.

All three companies have cloned animals, but from unborn cells, and all three are aiming to find the best way of producing proteins that are lacking in patients with genetic diseases such as cystic fibrosis.

By implanting the human gene that makes the protein into the chromosome of an animal, PPL and others have found they can generate significant quantities of the proteins from the animal's milk.

The process is still a hit or miss operation, however. Out of dozens of cloned animals, only one may yield a significant amount of the target protein. The aim is to clone that particular animal and get a herd of identical animals that will yield large quantities of protein-rich milk.

Even rivals admit the science that created Dolly was a formidable breakthrough. Company officials are disgruntled that the progress is not reflected in its share price.

"We have to congratulate PPL and the Roslin Institute for this development," said George Hersbach, chief executive of Pharming, a privately held company that made headlines in 1990 when it cloned the world's first transgenic bull, named Herman. "The commercial use is still a long way away, however."

This is why, analysts say, PPL's share price has been hovering close to its initial public offering price of 450p in recent weeks. While it surged as much as 65 per cent to a high of 552p after 24 February, the day Dolly hit the news, analysts say the share price now reflects the market view of the company's net present value.

"It's a massive scientific breakthrough, but translating it into cash is a few years off," said Stuart Rollason, an analyst with Panmure Gordon.

Meanwhile, PPL is pressing ahead in its bid to clone a cow, which may result in even better methods for producing new proteins.

"There will be a Nobel Prize for this, no question," predicted Thom Geimer, an analyst with Henry Cooke Lumsden.