1. Quotes of the Week
2. No controls on cloning or genetics in Canada
3. OF MICE AND MONEY - the bizarre world of bio-biz
4. ZOMBIE PIGS, CHICKENS AND QUAIL
for more on these topices see the ngin human and animal genetics pages at:
http://members.tripod.com/~ngin/gmhuman.htm
http://members.tripod.com/~ngin/gmanimal.htm
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1. Quotes of the Week
"Last night's vote makes it quite likely now that the first human trials, probably for a brain disease like Parkinson's, could take place in the next three years or so" -Simon Best of the Bio-Industry Association on the Lords vote on embryo cloning
"I think the possible benefits are very far in the future - they're entirely speculative. We don't really know if it's going to work. So I think it's a very distasteful kind of shroud waving to suggest that if we don't back this and rush along this scientific route people will not be saved next year or the year after. " - Tom Shakespeare, bio-ethicist specialising in disability and genetics, on the Lords vote on human emryo cloning
"Since 1990, when miracle cures were promised for 4,000 inherited diseases, between 300,000 and half a million human embryos have been destroyed or experimented upon. There have been no cures, but our willingness to walk this road has paved the way for more and more demand." - Lord Alton, speaking in the House of Lords debate on embryo cloning
"I wouldn't have any difficulty in eating a transgenic pig" - Professor William Muir of Purdue University who's developing "zombie pigs"
"The whole process of transgenics is fairly unpredictable and random, with downsides such as embryonic mortality and deformities.This is a dangerous route to follow." - Ben Mepham, executive director of the Food Ethics Council (see: item 4)
"Arts graduates couldn't change a light bulb." -Lord Winston on why we should oppose the "growing suspicion of science"
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2. No controls on cloning or genetics, groups claim: Canada has no laws to curb excesses in new technologies
Excerpts from Edmonton Journal Wednesday, January 24, 2001
Want to clone a human? Create a human-animal hybrid, say a human with pig-like qualities? An assembly line for designer babies? Come to Canada. This is one of the few industrialized countries, perhaps the only major one, that has no regulations to cover the new genetic and reproductive technologies that science has made possible.
Any use of the new techniques is technically permitted in Canada, because nothing has been legally prohibited...Some observers say the government sees little political gain to be had from introducing legislation that is bound to stir emotions.
``They just keep discussing and issuing papers,'' said Diane Allen, executive director of the Toronto-based Infertility Awareness Network. ``I know they've been really lobbied by those who don't want regulations.''
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3. OF MICE AND MONEY
An interesting insight into the bizarre world of bio-biz in the context of Alzheimer's, in this excerpt form the following article
St. Petersburg Times January 21, 2001, Sunday
STEPHEN NOHLGREN
Their altered genes doom them to dementia - but perhaps they will lead us to a cure for Alzheimer's. USF, with its rich mouse tradition, hopes to cash in.
Alzheimer's, which seems to strike randomly, presents a special challenge: If it is not passed from generation to generation, where's the genetic flaw? The dam broke about 10 years ago, when scientists at the University of London tested blood from an English family that suffered an extraordinary incidence of early-onset Alzheimer's. Family members all carried the same mutant gene. Researchers all over the world raced to get these genes into mice, but USF saw another opportunity - a chance to bolster its research reputation. It invited the English team to come work in sunny Florida . . . launching the university directly into the vortex of mouse politics.
Neurochemist John Hardy was regarded as the leader of the English team. Older than the others, he was a people person, an organizer and often the public spokesman. To lure Hardy across the Atlantic, USF awarded him its Pfeiffer endowed chair for Alzheimer's research. Also on the English team was Michael Mullan. With doctorates in molecular biology and psychiatry, Mullan was renowned for his theoretical creativity and astute lab work. He moved to USF first, in late 1991, while Hardy wrapped up work in London. The team already had identified the defective gene that had given an extra dose of a protein called APP to the English victims. Now a Swedish researcher shared blood samples from a family group in his country. Might both families carry the same genetic defect?
On arrival at USF, analyzing the Swedish samples was one of Mullan's first tasks. He took them to an off-campus lab and performed the sophisticated sequencing that located the mutation. It was on the APP gene, nearly identical to the English defect. Without consulting Hardy, Mullan filed a patent application - in his name only - that described how an Alzheimer's mouse could be created with the Swedish APP mutation. Mullan's superiors at USF had no problem with his unilateral move. The university had agreed not to lodge ownership claims against work carried over from England.
Mullan avoided any misunderstandings by conducting his blood work off-campus. But Hardy was less than thrilled that a member of his team had gotten a patent on his own.
"I was uncomfortable, but I went along with it,"Hardy recalls. "What I wanted was money. We agreed that any money (from the patent) would be used to support labs in Sweden and USF equally."
All Hardy says he wanted was whatever was in the best interest of researchers on two continents. But Mullan says Hardy is just posturing, that Hardy and other members of the team had tried to crack the genetic code on the Swedish samples but lacked the technical expertise. Hardy "didn't want to be on the (patent) paper,"Mullan says. "He hadn't done anything. He never suggested that he should be the inventor"or share in any royalties. In May 1993, their acrimony reached a comic-opera climax when Hardy discovered a letter that Mullan had left in the fax machine. It was addressed to a biotech firm in California. "It was good to meet with you the other day,"Mullan's fax said. "I thought that our scientific discussions went better than the business ones."
Hardy, worried that Mullan was about to cut some back-door deal, came back to the lab that night and removed about 350 blood samples from the refrigerator and shipped them, UPS, to colleagues back in England. The samples contained DNA from a newly discovered genetic mutation. In the morning, Mullan discovered the emptied refrigerator and immediately notified USF that the shipment might contain an infectious toxin similar to the one that causes mad cow disease. USF alerted the Federal Aviation Administration, which intercepted the shipment in Kentucky and warned the university that it could be fined up to $ 100,000 if the danger were confirmed. "We closed down the entire UPS operation in Louisville for one day,"Hardy recalls with chagrin. "I had FBI agents around my house and customs officials. My green card was threatened. It was exciting times."
Hardy's take was that Mullan was trying to make off on his own with what might turn out to be quite the scientific coup. But Mullan says that his business talks with the biotech firm were unrelated to any work going on at USF, and that Hardy's complaint about the fax was just "an excuse to shut down my lab - on no grounds whatsoever. He didn't like the fact that I was being successful."
A lawyer from USF drove the samples from Louisville back to Tampa. Mullan and Hardy continued their work - on separate floors - of USF's department of psychiatry. Their breakup was complete. "1993 was the worst year of my life,"Hardy recalls. "We had all arrived from England with high hopes and great plans to work together. It blew up in our faces."
So that was the state of affairs in the genteel field of academic research. Now we come to the dollars-first world of private enterprise. In February 1995, Athena Neurosciences, a California biotech company, announced that it had created the first workable Alzheimer's mouse. It carried the Swedish APP mutation, and its brain developed "amyloid plaques,"one of the two hallmarks of Alzheimer's.
That mouse was a pathfinder, but Athena did not share it freely with the academic mainstream. This was commercial research, where competition is the game and secrets the rule. In 1996, Athena was bought by Irish drug manufacturer Elan Pharmaceuticals, which kept the mouse to itself and began testing for possible cures. Meanwhile, University of Minnesota researcher Karen Hsiao announced that she, too, had created an APP mouse that carried the defective Swedish gene. Now all bets were off: The Hsiao mouse went to bid.
The Mayo Foundation secured licensing rights and began selling breeder mice to commercial drug manufacturers for about $ 800,000. Non-profit researchers, universities mostly, could get the mice for free - as long as they promised Mayo a crack at buying rights to any commercial product derived from the mouse. News of the Elan and Hsiao mice hit hard at USF, where mouse guru Karen Duff had been trying for two years to create a workable APP mouse. Duff, a junior member of the English team, had come to USF in the heady days with Hardy and Mullan. When the two heavyweight researchers had their bitter split, Duff had stuck with Hardy. With Mayo now controlling the APP mouse, Duff turned her attention to a different genetic mutation and hit pay dirt. Called PS1, the mutation controls a different element of Alzheimer's. USF promptly sold 15 of the Duff mice to Bayer Corp. for $ 350,000. Two years later, Karen Duff cross-bred her PS1 mouse with Karen Hsiao's APP mouse, producing offspring known as the Karen-Karen cross, or K2 mouse. It was a big step forward: Dosed with a double-whammy of genetic defects, the K2 develops a brain-load of amyloid plaque early in its life cycle. And it shows more clear-cut memory loss than other Alzheimer's mice - making it ideal for maze-running experiments. USF already has sold K2 breeding groups to three commercial drug companies for roughly $ 1-million and is negotiating a fourth deal. The university shares the K2 freely with other schools, with the understanding that USF might retrieve a cut if the mouse leads to huge profits. Elan Pharmaceuticals, which bred the first APP mouse, had hoped to keep Alzheimer's mice away from its commercial competitors - or at least control the split of any potential profits. Now, other drug companies were ignoring Elan and stocking up on descendents of Hsiao's APP mouse.
So two years ago, Elan sued the Mayo Foundation for patent infringement, saying that Hsiao had copied Elan's process.
But Mayo had an ace up its sleeve - the patent Michael Mullan had secured on his own back in 1992, the one that had stirred up hard feelings at USF. It had described, in theory only, how to create an Alzheimer's mouse with the APP mutation. Mullan never bred such a mouse, but Mayo had acquired the rights to his idea. Last summer, a federal judge ruled that Mullan's patent took precedence over the Elan mouse. Researchers all over the world could continue mouse experiments without Elan's lawsuit hanging over their results.
We still don't know how Alzheimer's works.
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4. ZOMBIE PIGS
James Chapman Science Correspondent
DAILY MAIL (London) January 24, 2001
SCIENTISTS are to create genetically modified farm animals devoid of aggression and stress. Work is already under way on 'zombie' pigs which will not bite and gore others in their herds. 'Aggression-free' chickens and quail are also being developed, and other animals could follow. But the ethical and animal welfare implications of the announcement has alarmed other experts. Anti-GM campaigners and the Royal Society for the Prevention of Cruelty to Animals said yesterday that the genetic modification of animals for commercial gain was unjustifiable. But the American scientists behind the project believe consumers will be happy to eat genetically altered meat within five years. 'I wouldn't have any difficulty in eating a transgenic pig,' said Professor William Muir, who is leading research at Purdue University, Indiana. 'We would just be talking about genes that change the expression of certain hormones connected with aggression or stress. 'There is a stress gene. There's a genetic test for it and it's very easy to remove it from the pig population.'
Professor Muir, director of Purdue's genome sequencing unit, said making pigs less aggressive could increase their growth rates by as much as 25 per cent. Professor Allan Schinckel, an animal scientist also working on the project, added: 'The more pigs you have in a pen, the slower their growth rate due to stress and aggression.'
The scientists have already pinpointed major genes for behaviour in mammals. If they can identify single genes involved in aggression in pigs, it may be possible to knock them out at the embryo stage. Alternatively, genes which produce chemicals such as serotonin - which are known to be important in regulating behaviour - could be added. As well as using this knowledge to create GM animals, they say a test to identify the 'aggression gene' would be of immediate use in traditional selective breeding programmes for farm animals. 'As soon as the gene is isolated, and if it looks as if we can correct it using genetic techniques, then we will go ahead and breed a transgenic pig,' said Professor Muir. He added that in a typical pig pen housing eight animals, there was an overall deficiency in growth because they were fighting for food. Some of the dominant pigs 'hog the trough' and eat more than they need. 'That's just nutrients going down the drain,' said Professor Muir.
The less aggressive pigs, meanwhile, don't get the nutrients they need and fail to grow to their potential.
'Another reason that the hogs don't grow to their potential is that when they are fighting, they produce lots of heat, which requires energy to produce,' he said. By using genomics techniques, Professor Muir says he believes he can alter this behaviour enough to see the 20 to 25 per cent growth increase. 'We've been able to use this method in quail to achieve more than a 200 per cent gain in growth,' he says. 'We know this isn't just pie in the sky.'
Academic Dr Ben Mepham, of Nottingham University, executive director of the Food Ethics Council, who has advised the Government's Agriculture and Environment Biotechnology Commission on the prospect of GM farm animals, said a lot of people would find the research 'completely unacceptable'. 'This would clearly be an offence to the dignity of the animals,' he added. 'The whole process of transgenics is fairly unpredictable and random, with downsides such as embryonic mortality and deformities.This is a dangerous route to follow.'
Vicky Robinson, senior scientific officer for the RSPCA, said: 'This research is really unethical. We should be addressing the causes of aggression, such as animals'living conditions, rather than trying to use genetic modification to get rid of it.'
Dr Patrick Dixon, an author and expert on cloning ethics, said: 'It raises huge questions. Will we start discriminating against people because they are genetically disposed to alcoholism or schizophrenia?' Dr Sue Mayer, of the campaign group Genewatchwarned: 'People will find this repulsive. 'We are just at the start of understanding the influence of genetics on behaviour and things like aggression are likely to be far more complex than just one gene. It's a slippery slope.'
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