Four cloned calves genetically engineered with human DNA and currently grazing in Iowa could hold the key to creating herds of identical cows that produce medicines in their milk and blood.
"Cows are ideal factories," said James Robl, president of Hematech LLC, which hopes to profit from drug-producing bovines. "Cows are big and have a lot of blood and produce a lot of milk."
Hematech of Sioux Falls, S.D., and its partner on the project, Kirin Brewing Co., aim to harvest groups of disease-fighting human proteins — called "immunoglobulins" — in cows. The protein groups are produced daily when the body comes under attack from foreign agents, and they're typically tailor-made to attack each invader.
The immunoglobulins hold great promise as medicines to treat a whole range of invaders from anthrax to earache-causing viruses in infants. Doctors already use them to treat such maladies as tetanus, rabies and even some cases of infertility.
Problem is, these proteins can't be grown in labs and factories and are available only from humans donors, limiting their supply.
In many cases, it's impossible to even get specific disease-fighters from human donors. For instance, the only way to obtain anthrax-fighting immunoglobulins is to infect people and provoke an immune response.
Hematech hopes to solve this problem by producing the proteins through purposely infected cows.
Other scientists have already spliced human genes into animals in the burgeoning field of molecular pharming. But those efforts have been limited to splicing a single human gene to produce a single protein to fight a specific disease.
Hematech and its Japanese research partner hope to coax their cloned creations to produce multi-protein products to attack a number of ailments.
Robl is a co-author of a research paper to be published next month by the monthly science journal Nature Biotechnology announcing the cloned calves' births and explaining their promise.
Here's what Robl and his colleagues did: They spliced two human genes that jointly produce the disease-fighters into a cow skin cell. The engineered skin cell was fused into a cow egg that had its nucleus removed. The resulting creation was coaxed into growing as an embryo and implanted into a cow.
Though the science isn't as controversial as human cloning or genetically modified food, Hematech's biotechnology still makes many uncomfortable and has raised ethical and safety issues.
Animal rights activists argue that cloning is inhumane and note that animal cloning has a high failure rate. Robl and his colleagues made 672 separate cloning attempts and only six resulted in live births. Two of the calves died within 48 hours.
Others are concerned about human safety, fearing that animal illnesses such as mad cow disease could be passed on to humans ingesting bovine-produce drugs.
There are also ethical considerations.
"No one is saying one gene in a cow makes it human," said Joseph Mendelson III of the Center for Food Safety. "But as some point we're going to start blurring the lines between species."
The center argues that not enough information is known about biotechnology to allow humans to consume genetically engineered products.
Robl said the cloned calves are better cared for than normal cows and that any drug produced in them would have to pass strict Food and Drug Administration scrutiny. The FDA has approved for human consumption several biotechnology drugs produced in Chinese hamster cells.
Hematech cloned its cows in Sioux Center, Iowa at Trans Ova Genetics, one of the nation's top cow-cloning companies.
The hope was that the human genes would activate in the cloned calves and begin producing the disease-fighting proteins. That happened in the four calves, but only in trace amounts because most of the human genes in the cows' cells didn't turn on. Instead, the complementary cow genes that produce the bovine version of immunoglobulins activated.
Still, the small amount of human protein found in the cloned calves' blood was viewed as a breakthrough.
"We have shown that it can be done," Robl said. "We've cleared a big first hurdle."
Robl said the next step is to engineer the cloned cows so most of the human genes will activate.
He and others are hopeful they'll produce human medicines in animals and plants, someday supplanting the need for large, expensive manufacturing plants now used by companies such as Genentech Inc. of South San Francisco and Thousand Oaks-based Amgen Inc. to produce biotechnology drugs.
In Vacacille, Large Scale Biology Corp. is working on producing anti-cancer drugs in tobacco while San Diego-based Epicyte Pharmaceutical Inc. is working on growing herpes-fighting human proteins in corn.
While Robl and others are optimistic they'll someday produce human medicines in cows, the technology is still many years from fruition with many obstacles in the way. Engineering the cows to produce more human proteins is a big challenge while cloning animals remains difficult.
Hematech would also need to assure the FDA the product it intends to sell is safe and completely cleaned of any cow molecules.
Hematech and its 20 employees provided the technology and the expertise for the cloning while Kirin put up $12 million to fund the project. Kirin, Japan's largest beer maker, jumped into the pharmaceutical business after it helped biotechnology Amgen build its "bioreactors" — large brewing vats — more than a decade ago.