Geneticists Modify Goats to Harvest Pharmaceuticals : Technology: Ability to produce large quantities of proteins in milk could cut costs of making medicines.
In a major advance hailed as the beginning of “barnyard biotechnology,” American and British researchers have genetically modified goats to produce large quantities of proteins in their milk that promise to sharply reduce the price of some medicines.
The ability to “harvest” pharmaceutical components from goat’s milk--and possibly from the milk of genetically altered cows and sheep--would streamline the costly process of manufacturing medicines through the use of biotechnology.
Currently, the biotechnology industry obtains the proteins necessary for making human medicines through an inefficient process that involves growing cultures in large laboratory vats of mammal cells that require constant monitoring.
Two industrial teams independently reported their results Monday in the journal Bio/Technology. Sheep, goats and cows could soon be “the reigning triumvirate of what could accurately become known as ‘barnyard biotechnology,’ ” an editorial in the journal said.
“We are very close” to producing commercially useful quantities of human pharmaceuticals, said physiologist Vernon G. Pursel of the U.S. Department of Agriculture in Beltsville, Md. “We may be there.”
A major advantage of producing pharmaceuticals in animal milk is that the concentration of desirable product is 100 to 1,000 times greater than in the laboratory cultures.
Animals also can produce many proteins that cannot be made by the bacteria commonly used in genetic engineering. Another advantage is that production can be increased simply by breeding more animals. Further, the animals do not have to be killed to obtain the product and require little special care.
Researchers have been working for at least 10 years trying to produce proteins in milk. Until now, the biggest success came in 1987 when scientists from Genzyme Corp. in Cambridge, Mass., and the National Institutes of Health reported they had produced a protein called tissue plasminogen activator (tPA) in the milk of mice. The protein is a clot dissolver that is used in treating heart attacks and strokes.
Now, molecular biologist John McPherson and his colleagues at Genzyme have used the same technology to produce tPA in goat’s milk.
They took the gene for tPA, attached it to a segment of genetic material that ensures the protein is produced only in milk, and injected the genes into fertilized goat eggs. The eggs were then implanted in surrogate mothers and allowed to mature.
That injection of the gene is the weak link in the process and is very much a hit-or-miss procedure. From 36 embryos implanted in surrogate mothers, 29 offspring were obtained and only one of them was a female that produced tPA in its milk. The female has since given birth to one offspring with the tPA gene, and researchers hope to breed a herd of animals that produce the pharmaceutical.
Although the goats described in the Bio/Technology paper produced relatively low quantities of tPA in their milk, molecular biologist Alan Smith of Genzyme said that animals born later yield as much as three grams of tPA per liter of milk. In comparison, laboratory cell cultures now used to produce tPA commercially yield no more than 0.1 of a gram per liter of growth medium.
In a separate paper, the Genzyme researchers reported that they had also developed a new technique for separating the drug from milk and purifying it.
Unfortunately for Genzyme, tPA probably does not have much of a future for the firm. Its medical functions can be filled by other products that are much less expensive, and its sales are sharply lower than analysts had originally predicted.
“But that really isn’t the point,” Smith said. “What we wanted to find out is, can you repeat with larger animals those things that we showed can be done in mice? . . . Now we can say, ‘Yes you can.’ ” Genzyme researchers are already working on production of other proteins that would have better marketing prospects.
In the second study reported in Bio/Technology, molecular biologist Alan Colman and his colleagues at Pharmaceutical Proteins Ltd. in Edinburgh, Scotland, followed much the same procedure as that used at Genzyme. They produced four female goats (from 152 embryos) that have a protein called alpha-one antitrypsin in their milk.
Humans born without the gene for alpha-one antitrypsin are at high risk for life-threatening emphysema. The 20,000 Americans with this disorder are now treated with alpha-one antitrypsin isolated from human blood plasma.
A remarkable aspect of Colman’s report is that alpha-one antitrypsin is produced at a concentration as high as 35 grams per liter of milk--meaning that it accounts for more than half the proteins in the milk. That high yield makes isolation very easy and should make the product much cheaper than the kind produced from blood plasma, said Ian Garner, head of the company’s molecular biology department.
Garner noted that Pharmaceutical Proteins is a very small company and that it hopes to license the process--or the animals--to a pharmaceutical company.
Barnyard Biotechnology
Researchers have fulfilled a long-time dream by using genetic engineering to create goats that produce human pharmaceuticals in their milk. Here’s how the process works:
1) Start with a gene for human protein.
2) Inject the gene into fertilized egg.
3) Isolate the fertilized eggs.
4) Transfer the eggs into a foster mother.
5) Test her offspring for human gene.
6) Mate goat carrying gene with another goat.
7) Establish a family of gene carriers.
8) Isolate the protein from the milk.
