Science & Technology: the clone arrangers
JAMES MORGAN June 27 2006
Copyright © 2006 Newsquest (Herald & Times) Discovery
Discovery
We are approaching the year 10AD. On July 5, 2006, 10 years will have passed since the birth of Dolly the sheep, the world's first cloned animal. Dolly, like so many celebs before her, died too young. But her creators at Edinburgh's Roslin Institute promised she would not die in vain. She was a martyr to modern medicine, the forebearer for a new breed from which we could "pharm" drugs for cancer, haemophilia and cystic fibrosis.
In 10 years, we were told, our farmyards would be full of clones. In the barn, modified pigs would be growing human organs for transplant. In the fields would graze transgenic sheep: living drug factories, whose milk was awash with human medicines. Alongside them, superior cattle, bred by cloned prize bulls to be bigger, more nutritious and disease free.
But, as we approach 10 years after Dolly, what progress have we made? Our restaurants, mercifully, do not serve up steak from cloned Aberdeen Angus cattle. Meat and dairy products from cloned animals are not yet licensed for sale in the UK or the US.
But neither, sadly, do our hospitals have a licence to prescribe medicines pharmed from sheep milk. And engineering pigs whose organs are compatible with our immune system has, thus far, proved impossible.
Meanwhile, a menagerie of weird and, some would argue, frivolous cloned creatures has appeared in the news. First, in 2002, was Snuppy the puppy, a cloned Afghan hound which succeeded only in creating a market for rich pet-owners who wanted to clone their precious pooch.
Next came two GM goats, Webster and Peter, whose milk contained spider silk proteins that could be purified and spun into a form of silk known as "bio-steel". A resulting herd of goats would, the US military hoped, be able to produce enough bio-steel to to manufacture body armour. But a few years later, the goats' developer, Nexia, abandoned the project.
More recently, two cloned mules, Idaho Gem and Idaho Star, caught our eye by winning races at a meeting in Midwest US. The experiment was funded by racing entrepreneur Don Jacklin, who offered scientists $1m to create a successor to his champion mule, Taz.
Clones such as these did little to persuade opponents of animal cloning, who argue it is an unnecessary and inefficient science.
So where are the giant leaps that Dolly promised us? There have been many minor breakthroughs, but this month, finally, came a landmark decision: approval for the first drug made in the milk of a genetically-engineered animal. The European Medicines Agency has agreed that A-Tryn (anti-thrombin), a human anti-clotting protein, may be harvested from the milk of transgenic goats. One in 3000 Americans suffers from a deficiency in anti-thrombin, which becomes dangerous during surgery or childbirth, when they cannot take conventional blood-thinning pills. The goats' creator, GTC Biotherapeutics, says it would take 90,000 donations of blood to produce as much anti-thrombin as one of its 1400 goats can produce in a year; $150,000 worth, to be precise.
The EMA approval is likely to persuade other firms to apply to license medicines. Nexia has engineered a herd of goats with milk containing an antidote for nerve agents sarin and VX. Another firm, PPL Therapeutics, a Roslin spin-off, has given hope to cystic fibrosis sufferers by engineering sheep to produce in milk a protein that reduces lung damage. And GTC claims it has 65 other therapeutic proteins ready to be manufactured in goats' milk.
But there is another experiment under way to create what would be the most exciting, useful and ingenious transgenic animal yet. The "Tc cow", engineered by Hematech, in South Dakota, will have an immune system that's half human, half bovine. Its cells will contain an additional artificial chromosome, with the genes for human antibodies.
The idea is that when the Tc cow is immunised with an infectious agent, such as botulinum toxin or MRSA, it will fight back by producing human polyclonal antibodies. These can then be purified from the cow's blood and given to hospital patients who cannot fight these infections because their own immune systems are compromised.
The Tc cow will offer enormous medical advantages. It will be more efficient and less expensive than present methods for generating human antibodies – cell culture – which can make only monoclonal (single variant) antibodies. Hematech has already created "Transchromic" calves, which carry the human chromosome. The final stage will be to "knock out" the equivalent bovine antibody genes, so the Tc cow produces purely human antibodies in its blood.
Assuming she remains healthy, the Tc cow will be a "living drug factory". She may never enjoy the cuddly celebrity status that Dolly did, but will be living proof that Dolly was a superstar worth celebrating.