Biotech Fish Safe for Environment, May Save Human Lives

Published November 1, 2004

Genetically modified (GM) fish may soon offer hope for people afflicted by a rare form of hemophilia and for patients suffering from internal bleeding.

An existing blood-clotting drug, NovoSeven, is produced by Novo Nordisk using GM hamster cells, but a single injection can cost $10,000. Right now, it is the only treatment available, although it is not approved for this purpose. Army medical staff in Iraq and other surgeons are using the drug to help stop internal bleeding and save lives under certain circumstances, according to an article in the September 11 New Scientist.

Wide Range of Medical Applications

Developed by Norman Maclean at England’s University of Southampton, in conjunction with Florida biotech firm AquaGene, the new method synthesizes human coagulation Factor VII in tilapia, a fast-growing freshwater fish widely farmed for food. Their approach could reduce the price of the blood-clotting agent significantly and make this life-saving technology much more widely available.

“It works by forming clots when someone has internal bleeding,” Maclean noted in the September 9 edition of BBC News online.

The GM cells offer promise beyond treating hemophilia. “I think the largest benefit will come from treating crash victims and people with gunshot wounds who have severe internal bleeding,” Maclean told BBC News.

“Blood transfusions and surgical measures to stop bleeding are essential in cases involving puncture or gunshot wounds or severe blunt trauma,” said Dr. Jeffrey Lawson, vascular surgeon and blood coagulation specialist at Duke University Medical Center. “However, due to defects in blood coagulation, bleeding sometimes continues. In these cases, NovoSeven or biotech Factor VII could be a valuable next step.”

The new technologies could play an even more valuable role in the treatment of bleeding from the gastrointestinal tracts of alcoholic patients suffering from fulminant hepatic (liver) failure, Lawson suggests. They could also help save the lives of mothers experiencing post-partum bleeding, a problem that occurs in 3 percent of all deliveries and may result in death, and to treat bleeding due to accidental overdose of blood thinner drugs like warfarin (coumadin), which are used to prevent and treat blood clots in stroke patients.

Advantages Over Other Treatments

Factor VII, a protein, can be purified directly from human blood, but doing so can transmit HIV and other diseases. Blood-clotting drugs based on mouse, hamster, or bovine proteins are known to cause allergic reactions in some patients. Coagulants derived from biotech fish may avoid these pitfalls, Lawson said.

Maclean’s team added a human gene to tilapia, inducing the fish’s liver to produce the protein and secrete it into the animal’s bloodstream. The researchers then remove the protein from the blood for transfer to human patients.

“Each milliliter of human blood has about 500 nanograms of the protein. We were able to match that yield in the blood of our fish,” Maclean noted in the New Scientist article. Within a year, he said, he hopes to increase the yield tenfold.

Risks Are Minimal

The research team also will have to convince regulators the fish-derived protein is the same as the human form; demonstrate the protein can be manufactured consistently at the same purity and potency; and show the fish-derived Factor VII is safe and effective. Although they have already tested it on blood samples from hemophilia patients, researchers will have to conduct many more studies before the protein is approved.

They also will have to overcome concerns by regulators such as the Food and Drug Administration’s (FDA) John Matheson, a veterinary medicine specialist whom the New Scientist article quoted as saying “escape is a concern,” even though the fish would be grown in contained facilities.

“Even if this were to happen and some GM fish ended up on dinner plates, several improbable events would have to occur for anyone to be harmed,” Henry Miller, a physician and former director of FDA’s Office of Biotechnology, said. Miller, a senior research fellow at Stanford University’s Hoover Institution, pointed out the protein would have to be present in the fish “at sufficient levels to exert direct toxicity or allergy.

“But there is no such thing as an overdose of Factor VII, and allergy is unlikely because Factor VII is a natural human protein,” noted Miller. “Moreover, the active agent would need to survive cooking, which destroys the biological activity of almost all proteins. It would also have to be orally active, which Factor VII is not.”

Miller also observed there is no evidence that transgenic or other fish can transmit any human disease to people. “Thus, the probability of any harm occurring to anyone is negligible,” Miller concluded.

FDA Remains Suspicious

Miller is concerned by what he calls the FDA’s “highly risk-averse” nature and its tendency to “keep raising the bar” for approval, especially for “innovations such as a novel technology or source for producing a new drug.” Even if Maclean’s team shows its Factor VII is safe and effective, many people might die unnecessarily before the FDA actually approves it, Miller worries.

It clearly will be some time before the product reaches the market. However, if the fish project becomes a commercial success, Maclean’s team and others will pursue additional innovations. “We have 20 other human therapeutic proteins that could be produced via fish to treat lung disease, liver problems, even tumors,” he told New Scientist.

Other research groups are exploring ways to produce proteins, vaccines, and other products from plants, chicken eggs, silkworm larvae, and cattle. Maclean believes fish deserve serious consideration as a source for such products because fish breed rapidly and can be farmed at relatively low cost, so production could easily be adjusted to meet demand.

Paul Driessen ([email protected]) is a senior fellow with the Committee for a Constructive Tomorrow and Center for the Defense of Free Enterprise, nonprofit public policy institutes that focus on energy, the environment, economic development, and international affairs.

For more information …

See “GM Fish Produce Cheap Blood-Clotting Agent,” New Scientist, available online at