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MSNBC Questions Dolly's Maker

Ian Wilmut, creator of cloned sheep, talks frankly   Dcotors Ron James, left, and Keith CAmbell, center, of PPL Therapeutics, with Dr. Ian Wilmut of the Roslin Institute and Dolly and Polly

PHILADELPHIA, Feb. 13, 1998 - Dolly, the cloned sheep who changed everything, turned 1 on Jan. 5. MSNBC took this opportunity to update our chat with Ian Wilmut, the embryologist at the Roslin Institute in Edinburgh, Scotland, who created her.

MSNBC: How is Dolly doing?
WILMUT: She is very healthy. She has had her wool taken off and, in the autumn, she was mated with a ram - the old - fashioned way. She is now pregnant. It is part of our plan to give her a healthy a life as possible. We don't really know how long to expect a ewe to live under well-protected circumstances, as sheep are normally put down commercially by the age of 6.

MSNBC: For many, cloning conjures up visions of duplicate Michael Jordans, or even multiple Hitlers a la "The Boys from Brazil". Has the response by the public and the media to your announcement of the cloning of Dolly been worse or better than you expected?
WILMUT: It's been very similar to what I expected - except there's been more of it. For us to be having a meeting with journalists about 1 year after the announcement of Dolly's birth shows just how immense the response has been. As for the tone of the response, I've been slightly disappointed in the public's rather limited concentration on science-fiction applications. If there were more interest in the potential beneficial applications, I would be more comfortable.

MSNBC: What are some of these potential beneficial applications? The paradox here in that the reason for doing the project was not to make groups of identical animals, but to be able to introduce a precise genetic change. The newborn animal would not be exactly like the source of the donor cells, in other words, but would carry a specific genetic modification.
WILMUT: At the present time, we simply can't make such genetic modifications in form animals, only in mice. Being able to do so would give us a chance to develop new health care products and to carry our research to study the role of specific genes.

MSNBC: What kinds of health care products can be produced from animal clones?
WILMUT: One use of the biotechnology would be to produce in the milk of farm animals proteins that are needed to treat human diseases, such as clotting factors for hemophiliacs or alphal anti-tryptosin for the treatment of emphysema and perhaps cystic fibrosis. This can be done at present time by the old method of gene transfer, but our targeted approach is much more predictable and reproducible - and would require fewer animals. A second application would be for donor organs. There is sadly a shortage of organs for transplant, so many people die before livers and hearts become available to them. One way of overcoming this is to modify pigs so their tissue is suitable for human transplant. Again, we can do this using the old method of gene transfer by adding a gene that slightly confuses the immune response. What gene targeting allows you to do is both add a gene and modify the surface of gene. We are confident that this dual approach will enhance the success of organ transplants between species.

MSNBC: Can you distinguish between the old method of gene transfer and the new gene targeting approach?
WILMUT: The old method of gene transfer involved injecting a few hundred copies of a gene into a nucleus in an early embryo. What people believe happens is that the movement of fluid associated with that injection causes breaks in the chromosomes, and the repair methods that then switch on to repair the chromosomes inadvertently include some of the broken genes in the chromosomes. If that is correct, breaks could occur in transfer genes and the function of the transfer genes could vary. Another limitation to this approach is that you can only add a gene, can't use this approach to modify a gene.

The new method depends on the fact that two similar strands of DNA tend to come together. If you identify a gene and copy and change it in the lab and then introduce that gene into cells, there is a tendency for the stands to come together - and the genes will actually change place in process of recombination. Since this method depends on the similarly of the stands, targeted modification is more efficient. There are fewer mutations - or even none - and you can add as well as change genes in a predictable manner.

MSNBC: How will clones help us to study specific genes? There are a number of genetic diseases in humans in which all that is wrong is mistake in a single gene. Best known is cystic fibrosis in which children have an accumulation of mucus in lungs and are particularly susceptible to lung infections. It's a very frightening disease for which there is no effective treatment.
WILMUT: The only way to try to develop new treatments is either to use human patients - and for safety reasons there's a limit to what you can do to a human - or to use mouse models of the disease. But, the respiratory system in mice is very different from that of a human. We are now collaborating to create sheep with the cystic fibrosis defect. This will allow us to better study the disease and to develop new drugs and methods for gene therapy. This is clearly a long-term project, but we believe it will offer some remedy for this disease. There are some people for whom this is unacceptable - who believe we shouldn't make an animal ill even if that brings forth a treatment for a fatal disease. Society needs to recognize this and make a choice as to whether we as a whole think it is acceptable. For myself, I would be willing to do it provided the sheep are kept under best possible circumstances to minimize the distress they suffer.

MSNBC: What's your greatest concern?
WILMUT: The idea of copying a person. There are still no reasons I would find it acceptable.

MSNBC: Will the basic scientific principles behind the creation of Dolly even work for cloning adults?
WILMUT: We simply don't know. But each child who is born should be treated an individual. If you make a copy of a person, you are saying that you don't want a child, but a person just like the one you're cloning. If you clone a running back, for example, you're saying to that child, "Don't be you, be a running back. "You're choosing his path for him.

MSNBC: Is there a theoretical application for cloning the dead?
WILMUT: If the cells have degenerated, as happens after a few hours, the technique simply won't work. While some have suggested you can keep the cells intact by freezing them, I don't believe that will work either. It's a sad way to mislead people. Theoretically, you could clone the just-deceased. But again, you are telling the child he will be a copy of a person not himself. And again that is ethically unacceptable.

MSNBC: How has your life changed since Doll's introduction to the world? Has the hysteria changed things?
WILMUT: It's both imposed an extra workload and also given us new opportunities. There's a continuous stream of people asking questions and making requests, which we can't always grant because of time, but also the opportunity to travel to meetings abroad.

MSNBC: Some have suggested that cloning of human embryos might help the most infertile of women. But you have publicly said you're against such clones. Why?
WILMUT
: Even if the woman has too few eggs, you could take an oocyte from a donor female and transfer that embryo. Cloning doesn't offer any opportunity you can't get from oocyte donation.

MSNBC: What was the first actual application?
WILMUT: We added genes to cells before gene transfer. Some of the ewes gave birth to lambs that secreted anti-hemophiliac factors in their milk. I'm confident we'll continue to see such applications.