GM organophosphate-resistant goats

Here's one way to cope with dangerous agrochemicals...

EXTRACT: "With Protexia, you would survive and be able to go back on the battlefield."

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Nerve gas antidote made by goats
BBC News, 24 July 2007
http://news.bbc.co.uk/1/hi/sci/tech/6912807.stm

Scientists have genetically modified goats to make a drug in their milk that protects against deadly nerve agents such as sarin and VX.

These poisons are known collectively as organophosphates - a group of chemicals that also includes some pesticides used in farming.

So far, the GM goats have made almost 15kg of a drug which binds to and neutralises organophosphate molecules.

Details appear in Proceedings of the National Academy of Sciences journal.

The drug, called recombinant butyrylcholinesterase, could be used as a protective "prophylactic" drug and also to treat people after exposure to nerve gas.

The US Department of Defense is funding the development effort by biotech firm PharmAthene to the tune of $213m (GBP105m).

It regards the drug as a promising way to protect its troops against exposure to nerve agents on the battlefield.

Butyrylcholinesterase could also be stockpiled for use in the event of a terrorist attack on a city with chemical weapons.

It is an enzyme that is made in small quantities by the human body.

The compound can be purified from blood, but the yields are poor.

However, the team at PharmAthene has been able to produce butyrylcholinesterase in large, commercial quantities and, the company says, at a reasonable cost.

Tough task

"It is a very difficult molecule to produce. There is a long history of people trying to produce this in everything from insects to yeast to bacteria and mammalian cells," said Dr Solomon Langermann of PharmAthene, a co-author on the PNAS paper.

"None of them has been able to produce anything beyond milligram amounts. In the goat, we can make two or three grams per litre."

The researchers inserted DNA for making the human form of butyrylcholinesterase into a "vector" molecule. This vector is then introduced into a goat embryo.

This allows the human gene to be incorporated into the goat's DNA sequence. The resulting female animals, all healthy, produced large quantities of butyrylcholinesterase in their milk.

The high yields are partly down to "control elements" - stretches of DNA added, along with the human gene, to the vector molecule.

These control elements regulate how much of the enzyme the goat produces and ensure that most of it is produced in the milk, rather than in other tissues.

Safety trial

Once the enzyme was purified from milk, the scientists injected it into guinea pigs, and saw that it remained active in the bloodstream.

The commercial name given to the butyrylcholinesterase enzyme is Protexia.

Dr Langermann said that Protexia was more effective than the combination of the drugs atropine and 2-PAM currently carried by soldiers for protection against nerve agents.

"Those (older) drugs get cleared from the blood very rapidly. Even if the soldier were to survive, they would have very severe neurological damage," he told BBC News.

"With Protexia, you would survive and be able to go back on the battlefield."

It is also effective against a variety of different organophosphate poisons.

The product is still several years from entering use; it needs to pass a safety trial and seek approvals from the US government.

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