Peer finds way to modify man

December 1, 2000

Powerful techniques to create transgenic animals and humans and to isolate stem cells from their tissue have been patented by Lord Winston, the Labour peer and Imperial College scientist.

The new techniques involve altering sperm, rather than eggs, as in current methods.

The methods represent important advances in current technology and could be used in the development of a wide range of therapies, from preventing parents with genetic disorders passing them on to their children to the creation of transgenic animals with organs suitable for human transplantation.

As scientific tools, the techniques will help scientists study the influence of genes in many diseases and will boost research into stem cells without the need to use material from embryos, such as the creation of replacement tissue and organs.

According to the patents, the approaches could also be used to genetically engineer farm animals and other vertebrates more effectively than is currently possible and help conserve endangered species such as rhinoceroses and tigers.

One patent states: "The technology is of great value in the study of stem cells and cellular development, and in producing transgenic vertebrate animals as well as for repairing genetic defects. The present technology is also suitable for germ line and stem cell line therapy in humans and other vertebrate animal species."

Despite removing the need to obtain stem cells from embryo tissue, the research does raise the more troubling ethical dilemma of deliberately altering the human germ line - an individual's genetic code that is passed to their offspring.

One of the patents says there is "a need for a way of selecting or isolating stem cells from non-stem cells, for study or therapeutic uses, that does not require the use of embryonic material, because the use of embryonic material may present ethical problems".

Lord Winston has been critical of the delays researchers have faced as the government considers whether stem cell research using tissue from human embryos should be permitted.

He has also advised caution on the possibility of the genetic manipulation of humans, admitting there were grave risks but suggesting it was a prospect that deserved to be discussed.

The research outlined in the patents is the product of a collaboration between Lord Winston, professor of fertility studies at Imperial College, London, and chair of the House of Lords science and technology select committee, and Carol Readhead, Carsten Muller and Phillip Koeffler at the Cedars-Sinai Medical Centre in Los Angeles.

In addition to the techniques involved, the two patents, which were published in May, cover an engineered human genetic sequence, those cells that carry it and the transgenic nonhuman animals produced with it. As the research has yet to appear in a scientific journal, Lord Winston declined to discuss it further.

The techniques on which the patent is based offer a simple, less expensive and less invasive method of producing transgenic animals than exists at present.

Transgenic animals have previously been produced almost exclusively by injecting new genes into fertilised eggs. However, this is inefficient, requires large numbers of eggs for success and can be prohibitively expensive, especially when working on large animals comparable to humans.

Lord Winston's method, mentioned in his recent BBC television series Superhuman, involves engineering the genetic code of male germ cells that produce sperm. Both patents describe a way to extract these germ cells so that their genetic code could be engineered in vitro and then returning them. Alternatively, new genetic material could be injected directly into the animal's testicles.

Such engineering would alter the germ line of an individual, enabling him to pass the new genes to his transgenic offspring.

One of the patents also describes how animals could be engineered so that specific sorts of stem cell produce a green fluorescent protein or similar substance. They could then be isolated and studied.

In a series of experiments, many of which have been performed in the United States, the scientists said they had used the techniques to create five male transgenic mice that produced green fluorescent protein in their germ cells.

The scientists believe that the approach could also be used to isolate a wide range of other types of stem cell, from embryonic to brain and liver stem cells.

Lord Winston will join other scientists for a one-day symposium on the science of stem cells at Chelsea and Westminster Hospital, London, on December 6, to mark the first anniversary of the Imperial College Tissue Engineering Centre.

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