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 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."
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The Independent - United Kingdom;
BY WORDS BILL TUCKEY