Animals with human genes aren’t a novelty. Over the last few years gene splicers have, for instance, created sheep with human growth hormone and pigs with insulin in their blood. But harvesting the drugs requires killing the animals–a waste of the effort and expense it takes to engineer them. So when, in 1987, researchers slipped a human gene into mice so that they produced a human protein in their milk, “molecular pharmers” saw their chance:
Researchers at Tufts and the Genzyme Corp. of Cambridge, Mass., engineered goats to produce tissue plasminogen activator (t-PA), a protein that dissolves blood clots and extends the lives of cardiac patients. The scientists injected human genes for t-PA into fertilized goat eggs (diagram) and implanted the hybrids into surrogate mothers. Of 29 offspring, one male and one female were “transgenic”: they carried the human gene. After breeding the female (the old-fashioned way) to induce lactation, researchers isolated and purified t-PA from her milk. One of her five kids was also transgenic. One goat produces up to three grams of t-PA per liter of milk. Biotech firm Genentech, which makes a prescription-drug version of human t-PA in huge fermentation vats, charges $2,200 for a .1-gram dose, partly to recover research costs.
Using similar methods, scientists at Pharmaceutical Proteins, Ltd., in Edinburgh, Scotland, produced sheep with the human gene for alpha-1-antitrypsyn. (About 20,000 people in the United States have genetic defects that keep them from making this protein, whose absence can cause deadly emphysema.) Five of 112 lambs carried the human gene. After maturing and reproducing, one ewe made 70 grams–$70,000 worth–of alpha-1 a day.
Scientists at the University of Leiden in the Netherlands and at Gene Pharming Europe, also in Leiden, used analogous techniques to make transgenic cattle without surgery. Of 103 embryos injected into foster mothers, 19 calves were born. One male and one female had the human gene, used in this experiment only as a marker.
One obvious problem with barnyard bioengineering is the low rate of success. Only two of 103 doctored cow embryos, for example, carried the human gene. The reason is that the gene finds its way into the egg’s DNA at random, or not at all. At some insertion sites the gene lies dormant. The Tufts team is therefore trying to flank the human gene with special DNA “switches” that will enable it to produce the desired protein no matter where it sits. Another hurdle is to make the test-tube animals pass the gene to at least half their offspring. Then scientists could dispense with test-tube embryos and surrogate mothers.
Finding another way to exploit livestock doesn’t sit well with animal-rights activists. At least the human protein does not seem to affect mating or behavior, and there is good reason to keep herds happy and healthy, in barnyards, and not factories: stressed animals produce less milk. Says Henry Spira, a New York activist for reforms in agriculture, “If this gets the industry to focus on the well-being of animals, it would be a welcome omen.”
Barnyard drugs are at least five years from commercialization. Approval by the Food and Drug Administration will require proof that the protein is not contaminated with animal viruses or other proteins. The molecular pharmers don’t expect that to be a problem. So cherish the sheep and cows in our midst: they soon may offer us not only food and clothing but medicine, too.
Giving animals human DNA is becoming routine.
Human gene for t-PA is spliced into DNA that is activated during lactation, then injected into goat egg.
Some of the eggs implanted into surrogate nannies develop into kids that carry the t-PA gene.
After mating, the carrier produces human t-PA during lactation. t-PA is then isolated from milk and purified.
