For Cloning Pioneer, Biotechnology Holds Promise of Medical Gains

Dolly, the world’s most famous sheep, is indisposed, having just given birth for the third time in as many years.

Ian Wilmut, laboratory father of the first mammal cloned from an adult cell, is somewhat more available, seated next to a computer that is flashing the time. The digital seconds fly off the screen at a heart-palpitating rate.

Time is of the essence for both members of the cutting-edge Roslin Institute since Dolly heralded a biological revolution three years ago. In the sheep’s case, the concern is with signs of premature aging that scientists are unable to explain. She looks healthy to an examining vet, but under the microscope, a part of her chromosomes is seen to have shortened more than is normal for her years.

What does it mean and will it lead to an early death? No one knows yet.

Wilmut’s preoccupation, meanwhile, is with all of the pressure that Dolly’s fame has put on his time: the speeches, interviews and inquiries competing with demands for more research to push the frontiers of biotechnology even further.

More than most scientists, the bald and bespectacled embryologist has had to respond to the enormous moral questions and brave-new-world fears raised by his groundbreaking work in genetic engineering and cloning: Is it right to tamper with nature? Are we headed for human cloning? Should companies be allowed to patent genes and DNA, the basis of life?

At the same time, he has fielded heartbreaking telephone calls from parents wondering if it is possible to clone a young child who died. As the son of a diabetic who was blinded and crippled by the disease, Wilmut feels an urgency to discover biological cures to such illnesses. He knows too that thousands of kidney and heart patients are desperate for scientists to develop an animal whose organs are fit for transplanting to humans.

“From the first time man put a sharp stone to a stick, he could use this as a tool to eat with or as a weapon to kill people,” Wilmut said. “It’s not a dilemma--it’s a fact of life. We have to get used to making these choices.”

Wilmut is taking time to talk because he feels strongly that the public must be educated about the new science and technology to make informed policy decisions. To that end, he wrote “The Second Creation” with Keith Campbell, his scientific partner in cloning Dolly, and author Colin Tudge.

The book, to be published in the United States in June, is textbook dense and complicated. Wilmut, on the other hand, is pleasantly plain-spoken.

“We want to promote discussion of the potential uses of the technology. We profoundly believe that these are social decisions that should not be left to the scientists, the companies, the doctors and the patients, who are all too involved,” Wilmut said.

Before Dolly was cloned by destroying the nucleus of an adult sheep cell and replacing it with another nucleus, scientists believed that such a procedure was “biologically impossible” in mammals. Dolly rendered that term obsolete and showed that future limits on such technology would be determined not by biology but by ethics.

The moral and emotional complexities of biotechnology were driven home to Wilmut immediately after the announcement of Dolly’s birth: The German magazine Der Spiegel accompanied its report with a cover illustration of a regiment of cloned Hitlers.

One of the most persistent misconceptions of this technology is that clones are identical, Wilmut says. They are not, as was proved by Roslin’s four cloned rams--Cedric, Cecil, Cyril and Tuppence, who are genetically identical but different in size, color and temperament.

Here again, scientists do not know why. One possibility is that the nuclei from which they were created were placed in egg cells from four ewes and thus developed in distinct environments.

“I often tell people that a genetic copy of Saddam Hussein might well turn out to be a nice guy,” he said.

No regiment of Hitlers; no army of Einsteins either.

Wilmut finds the idea of human cloning abhorrent, although he is only too aware of his role in making it possible. There is no medical justification for attempting human cloning, he says. He believes that it would be “grossly irresponsible” to consider trying to clone a human, given scientists’ lack of expertise in the field and the lack of knowledge about what it means to be a clone.

Most cloned sheep embryos die, many of them after having developed serious deformities. Only 1% to 4% of reconstituted embryos survive to become live offspring, Wilmut says. Of those, 20% die shortly after birth--four times as many as in a naturally bred flock.

Then, there are the unknowns about life as a clone. Dolly is an apparently healthy, if spoiled, ewe who has delivered normal offspring and who would ordinarily live about 12 years. What do the shortened ends of her chromosomes mean? One possibility is that she will be more vulnerable to tumors than are normal sheep.

Wilmut has three grown children of his own and a 1-year-old grandson whom he clearly adores. He can understand a parent’s willingness to try anything to save--or replace--a child. But he wouldn’t push the limits of biotechnology even for his own family.

“The image is that you bring a child back. You don’t do that. My daughter is a flute player and active Christian. A copy of her might not be either one of those things,” he said, adding that to try to make a baby into the person someone else was would be a tragedy.

So what does Wilmut consider to be the legitimate pursuits of biotechnology? Improving livestock, certainly. Cell therapy, substituting healthy cells for diseased ones to treat the likes of diabetes or Parkinson’s. Maybe even organ transplants, although Wilmut says they are a long way off despite the recent birth of cloned quintuplet pigs--the most likely species to become organ donors.

Scientists already have created animals fitted with human genes to produce proteins in their milk that can be used for treating diseases such as emphysema, cystic fibrosis and hemophilia. The therapies are still three to five years from coming on the market, Wilmut says.

PPL Therapeutics, the commercial pharmaceutical company located on the grounds of the government-funded Roslin Institute, announced last month that it had created the first cloned pigs, offering hope of farming animals for organs such as hearts and kidneys to transplant into humans.

The pigs must be genetically altered so that their organs will not be rejected by a human body, and countless tests must be done to ensure that dormant viruses would not be passed on to humans. The company says human trials could begin in as little as four years. Wilmut says six to 10 years is more realistic.

And then what? Human cloning is illegal in the U.S. and Britain, but is it the logical next step? Will there be a commercial drive for human cloning one day?

Most of the investment in biotechnology research comes from companies hoping to profit from cellular therapies and organs. The Roslin Institute and the government agencies that funded its cloning research own the patents for the technology that led to Dolly.

Roslin formed a commercial affiliate, Bio-Med, that merged with the California-based Geron Corp., which is licensed to exploit the cloning research for its program to create replacement tissues and organs. Wilmut volunteers that he has stock in Geron and stands to earn a lot of money from new breakthroughs in biotechnology.

Thirty years ago, scientists like Wilmut would never have mentioned the word “patent,” he said. “Now, I have a contractual obligation to think of patents.”

Many people believe that these technologies should not be patented because they revolve around the makeup of human life. Others worry that the patents for controversial procedures are being given to private companies governed by commercial, rather than ethical, interests.

President Clinton and British Prime Minister Tony Blair have called on companies to give free access to discoveries on the makeup of the human genetic code. People have 60,000 to 80,000 genes, but scientists know what only a few thousand of them do. The faster the genes are identified, the more likely new drugs can be developed to treat diseases.

Wilmut says governments need to clarify what can and cannot be patented. He believes that it is inappropriate to patent a list of genes but reasonable to patent the inventive use of a gene for producing proteins needed to treat diseases. A patent ensures both a return for investments in biotechnology and quick dissemination of scientific information, he argues.

Scientists can then build on the information to “take humanity into the age of biological control,” as Wilmut and Campbell state in their book.

But that does not answer the question of whether all of this is likely to lead to human cloning.

Wilmut, a middle-class Englishman who looks like a high school teacher, is an ordinary man who has done something extraordinary. He responds carefully that the technology for human cloning does not exist yet and that he hopes scientists will not go down this road. But that is probably a futile hope, he acknowledges.

“Is it inevitable that cloning will be used to copy a person? No, it’s not inevitable,” he said. “It all depends on what societies decide they want to do. Is it likely it will happen? Yes.”