More MS news articles for Jan 2002

Phreak of Nature

Cows that produce cancer-fighting milk, pigs bred for human organ transplants and plants that treat lymphoma. `Pharming' might be possible, but do we really want to go there?

Jan 19, 2002
The Independent - United Kingdom;

The strange and, some would say, sinister world of genetic animal experimentation has been back in the headlines this year already. First there was the birth of a litter of piglets with transplant-friendly organs. Then there was the news that Dolly, the first ever cloned sheep, has prematurely contracted arthritis. Both stories prompted calls for an end to the kind of biological tampering that created these creatures, but the ethically concerned shouldn't hold their breaths.

The fact is that the technology behind Dolly and friends is ushering in a whole new branch of medicine, called "pharming", in which human genes are added to animals or plants to create medically useful products. "Immunocows", "golden eggs" and "plantibodies" are just some of the buzzwords flying around in an industry with the potential to earn billions for the drugs companies involved, who are fighting each other tooth and nail for patents to the technology. Among the prospects being held out by scientists in the field are new treatments for diseases including cystic fibrosis, arthritis, HIV/Aids and even cancer.

One of the main players is a British company called PPL Therapeutics, a commercial spin-off of the government-funded Roslin Institute in Edinburgh (creators of Dolly). PPL is licensed by Roslin to exploit some of its biotech discoveries. It was PPL who announced earlier this month that it had produced cloned "knock-out" pigs - with the gene which makes the human body reject their organs removed. Humans are sometimes referred to as as "vertical pigs" in medical circles, because our internal organs are so similar, but pig-to-person transplants are still a long way off due to the danger of pig viruses jumping into humans.

What PPL is betting its bottom dollar on, though, is another technique pioneered by Roslin, in which scientists inject the fertilised eggs of sheep or cows with human genes that produce disease-fighting proteins. The resulting "transgenic" offspring secrete these proteins in their milk, which are then processed into drugs.

One such protein is AAT (Alpha-1-Antitrypsin), a treatment for emphesyma and cystic fibrosis that is now in trials at 12 hospitals in Europe, Canada, Australia and New Zealand. PPL has gone into partnership with the German drugs giant Bayer and is investing pounds 42m in a huge production plant to manufacture it. The company expects to have genetically engineered AAT on the market by 2005, and believes that 150,000-200,000 emphesyma sufferers in the US and Europe could benefit from it. At present, Bayer extract AAT from human blood and consequently it is in short supply.

AAT will be the world's first "pharmed" product, but according to Roslin's Dr Bruce Whitelaw: "If the clinical trials are successful then you'll start to see more pharmed drugs come on to the market fairly quickly. From 1986-1991 the focus was on researching the new technology, then there was 10 years of development. Now the time-lag is over."

PPL's herds of genetically modified sheep and cows are already being milked for a variety of human proteins, including BSSL (bile salt stimulated lipase, usually found in human breast milk) now in clinical trials as a treatment for pancreatitis.

The US government is also funding the company to develop "immunocows" which generate cancer-fighting human antibodies, while elsewhere, a partnership between Roslin and the US firm Viragen is investigating the possibility of genetically engineering chickens to produce "golden eggs" with similar anti-cancer properties.

PPL's biggest competitor is the US company Genzyme Transgenics, who work mostly with goats. It is is currently evaluating proteins-in-milk treatments for Crohn's disease, rheumatoid arthritis, HIV/Aids, lung cancer as well as developing a malaria vaccine.

Indeed, the list of potential treatments taking advantage of this technology is huge, covering everything from multiple sclerosis to leukaemia, diabetes to Parkinson's disease, strokes to muscular dystrophy. But many are yet to be tested or are still in the very early stages of development. As Dr Whitelaw points out: "Much of the research is being carried out by commercial companies chasing funding, so you have to be careful about the claims they're making."

The precariousness of this fledgling industry was highlighted in August last year when one of its main players, the Dutch company Pharming, went into receivership. Pharming ran into money trouble after a series of legal dogfights with PPL and Genzyme Transgenics over patents.

Meanwhile, down on the pharm, another branch of gene-splicing technology is promising equally revolutionary possibilities.

While the furore over so-called "Frankenstein food" has shown the public to be wary of eating genetically modified crops, it hasn't stopped a number of biotech companies, mostly in the US, from experimenting with "molecular farming" - extracting medicines from crops spliced with human genes.

One company, Epicyte Pharmaceuticals, is attempting to make the Pill redundant by growing "contraceptive corn" for humans and implanting it with a genetic defect found in some women that kills sperm.

Elsewhere, Australian scientists have introduced a measles gene into f tobacco, which could lead to the creation of an alternative, inexpensive vaccine for the disease. Tobacco, a plant responsible for the death of millions, is also the subject of experiments to produce antibodies, or "plantibodies", against diseases including, ironically, cancer. The stakes are high, with the antibody drug market expected to be worth some pounds 5bn by 2004.

None of these plant-generated proteins have yet come on the market, but human testing is already under way for one such treatment, for non-Hodgkin's lymphoma, produced by the US firm Large Scale Biology.

These developments are being anxiously monitored by environmental groups. In September Greenpeace activists staged a protest in a field in California (above) where trials of genetically engineered rice containing human genes were being carried out. "There is just no excuse for allowing drug-producing crops to be grown in fields where they can contaminate the environment and food chain by spreading their genes to wild relatives and conventional crops growing nearby," says Kimberley Wilson, a genetic engineering campaigner for Greenpeace USA.

The company behind the trial, Applied Phytologics, had complied with US government safety rules by planting a four-foot wide "buffer zone" of normal rice around the field and has insisted there is no danger of wider contamination. Greenpeace, however points to the recent Starlink fiasco in the US, in which that company's genetically engineered corn, approved for animal feed but not human consumption, was found to have cross-pollinated widely, prompting nationwide recalls of taco shells, corn chips and other foods.

The prospect of a similar accident with contraceptive corn, say, is certainly a frightening one. Nevertheless, for companies involved in GM crop experiments, one of the selling points of their products is that the ethical issues are not as complex as with livestock-based pharming.

Greg Rees, a campaign manager for Compassion in World Farming, spells out some of these concerns: "In the process of producing transgenic animals, only a tiny proportion of embryos survive. We don't believe it's ethically right to engineer sentient beings, to turn them into factories for a non- vital need - these proteins can be produced in other ways, it's just that they are more expensive."

Scientists involved in pharming disagree, arguing that while some proteins can grown in vat-like "bioreactors" using genetically engineered bacteria or cell cultures, others are either too complex or needed in too large a quantity to be made without an animal host.

April D'Arcy, a spokesperson for PPL, says: "We feel our work is justified by its benefits. It is true that there are deaths in the initial stage of creating transgenic animals. But once we have made the founder animals, their offspring are bred in the normal way and have a wonderful life. We are licensed and inspected rigorously by the Home Office and we also have our own strict ethical rules."

"Our view is simply that we're trying to help people," says Tom Newberry of Genzyme Transgenics. "We have an ageing population, and there's a crying need to give them a better quality of life."

Debates over ethics will no doubt rumble on, and the next few years will also prove crucial in determining just how many of the pharming community's claims are achievable - in separating the cash cows from so much genetically modified bullshit. Dr Whitelaw has perhaps the most realistic, if cynical, take on the future: "It's not ethics that will determine how this industry goes forward," he says, "it's economics." E

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