Researchers Look to Milk for Drugs of the Future
If some bioengineers have their way, cows, goats and sheep could become drug factories of the future, producing pharmaceutical products from their milk at a fraction of the cost of traditional methods.
Integrated Genetics Inc., a leader in this area of research, has already produced the costly drug, tissue plasminogen activator (TPA), in the milk of mice and is now experimenting with goats.
If the Framingham, Mass., company is successful, it believes the cost of treatment with TPA could be reduced to $200 a dose from the current $2,000 and create a $1 billion a year market for the medicine.
Virtually any protein-based drug could theoretically be produced in milk. However, even the most optimistic researchers do not expect drugs produced from milk to be commercially available for at least four to five years.
The ideal manufacturing vehicle, the cow, may not be possible for several years beyond that.
Still, there are few who doubt the feasibility of the concept. “There is nothing that tells me that if can’t work,” said Alain Schreiber, vice president of discovery at the pharmaceutical giant Rorer Group.
Schreiber concedes that the feasibility of producing drugs in dairy milk has yet to be proved but said, “Here at Rorer we are doing a lot of research and development work, spending a lot of resources on the concept. We wouldn’t be doing that if we were not enthusiastic.”
The rising price of producing bioengineered drugs such as TPA, which is used to prevent heart attacks, has encouraged the industry to seek new ways to mass-produce the drugs.
Costly Reactors
Currently, they are produced in costly bio-reactors that act like large fermenters containing cell cultures or genetically engineered microorganisms. Genentech Inc., which markets TPA, spent about $100 million building its bio-reactor.
In November, 1987, Integrated Genetics, working with National Institutes of Health scientists, announced that it had successfully fused the mouse gene that regulates formation of milk with a human gene coded for TPA.
The hybrid gene was then injected into fertilized mouse eggs that were implanted in “foster mother” mice that brought the embryos to term. The female offspring successfully secreted TPA in their milk and passed along the trait to successive generations.
Alan Smith, scientific director of Integrated Genetics, said the process in some ways produced a less problematic product than other altered animals, such as the famous “Harvard Mouse” patented by Harvard University last year, because the entire animal is not changed.
Only the milk is different, causing no harm to the animal or its offspring.
Mice are still not a practical way to produce drugs, however, because the amount of milk they make is so small. But several companies and universities are experimenting with larger livestock with a much greater potential.
Tufts University Experiment
Integrated Genetics has just started a three-year experiment with Tufts University to produce TPA in goats. Smith estimates that the goats should be able to produce about 10 grams of the medicine per liter of milk, compared to 10 milligrams per liter of cultured cells in a bio-reactor.
In Scotland, Pharmaceutical Proteins Ltd. is producing Factor VIII, a drug used to treat hemophiliacs, in milk from bioengineered sheep, although only in minute quantities.
But the greatest promise is cows, because of their voluminous milk-producing capacity. “I’ve read some estimates that a herd of 30 to 50 cows could supply enough Factor VIII for the entire world,” said Richard Godown, president of the Industrial Biotechnology Assn., a trade group.
Cows are considered the ideal vehicle for drug production because of their voluminous milk production and the unique nature of their udders.
“The udder is the perfect place for introducing drugs because nothing passes through it into the bloodstream,” said Bob Wall, a reproductive physiologist with the U.S. Dairy Assn.’s Agricultural Research Service.
Bovine Problem
The problem with cows, however, is the long gestation period, It takes three years to bring a bovine embryo through birth to maturity, and several generations must be bred to ensure that the drug-secreting trait is being passed on.
But, said Wall, cows have the potential for producing far greater quantities of some drugs than are available with any other method.
Rorer, for example is doing research on producing albumin, the main protein in blood plasma, in cows and other livestock. Large infusions of albumin are often required by patients after major surgery, and currently can be obtained only from human blood plasma.
The cost of obtaining blood plasma can exceed $20 a liter, said Rorer’s Schreiber. “A liter of milk is less than $1 at the supermarket,” he said.
