Genetically modified fish may help treat hemophiliacs

A human blood-clotting factor used to treat some people with haemophilia and accident victims suffering serious bleeding has been produced using genetically modified fish.

There is still a long way to go before any product reaches the market, but if the fish project is a commercial success many other proteins might be made this way. "We have a list of 20 other human therapeutic proteins that could be produced via fish to treat lung disease, liver problems, even tumours," says Norman Maclean of the University of Southampton in the UK.

Maclean has been working on producing human coagulation factor VII in fish together with AquaGene of Alachua, Florida. Factor VII can be purified directly from human blood, but there is a risk of diseases being transmitted this way. The only alternative, called NovoSeven, is produced using genetically modified hamster cells. But growing mammalian cells is very expensive, and the cost of a single injection can be as high as $10,000.

Factor VII is used to treat people with a rare form of haemophilia that means they cannot make the protein themselves, and it is often needed to treat other forms of the disease as well. Many doctors, including US army medical staff in Iraq, are now also using it to stem internal bleeding caused by accidents or gunshot wounds, even though NovoSeven is not approved for this purpose.

AquaGene is hoping to produce a much cheaper rival product using tilapia, a fast-growing freshwater fish widely farmed for food. Maclean has now managed to produce several lines of transgenic tilapia that produce human factor VII. His team added a genetic switch from the tilapia to the human gene. This ensures that the gene is switched on in the liver of modified fish, and the protein secreted into the blood.

"Each millilitre of human blood has about 500 nanograms of the protein. We were able to match that yield in the blood of our fish," says Maclean. He hopes to produce tilapia that make 10 times that level within a year.

The next step will be to convince regulators that the fish-derived protein is the same as the human form, and that it is safe. The researchers have already tested it on samples of blood taken from patients with haemophilia, but many more studies will have to be done.

Other groups are exploring rival ways of producing proteins, from plants and chicken eggs to silkworm larvae and cattle, but Maclean thinks fish are a serious contender. There is no evidence that any disease can be transmitted from fish to humans, for starters. Transgenic fish are also relatively cheap and easy to make, whereas it can cost millions to produce transgenic cattle.

Because tilapia breed so quickly, production could easily be adjusted to meet demand. "But escape is a concern," says John Matheson of the US Food and Drug Administration. For commercial production, transgenic tilapia could be grown in contained facilities.