ROANOKE TIMES
Copyright (c) 1997, Roanoke Times
DATE: Sunday, April 6, 1997 TAG: 9704040087
SECTION: BUSINESS PAGE: 1 EDITION: METRO
DATELINE: BLACKSBURG
SOURCE: MARK CLOTHIER THE ROANOKE TIMES
Let's say you have a company that makes something.
Let's also say the way you make this product - your production process - is a little less than efficient.
Just 10 percent of what you produce is good enough to use.
This means that for every 100 finished products that roll off the production line, 90 are trashed.
If you're Blacksburg's PPL Therapeutics Inc., even though you have state-of-the-art technology to make proteins for medicine, you're still operating at about 10 percent efficiency. This is why news in February that a sheep had been cloned in Scotland was huge for the company.
It also was fairly large news for everyone else. Dolly the sheep clone - tangible proof that the process worked - landed on the front page of newspapers around the globe, on the cover of Time magazine and prompted ethical discussions at water coolers everywhere.
But for Blacksburg's PPL Therapeutics, Dolly meant the company was that much closer to perfecting a cloning process for cows. That achievement would make the Blacksburg company a very efficient and, potentially, very profitable outfit.
What the company hopes to make are proteins, to be sold to large pharmaceutical manufacturers and small biotechnology companies and used to fight disease in humans.
The biotech drug industry, the use of living cells to make drugs, took off in the late 1980s, said Alan Goldhammer, director of technical affairs for the Biotechnology In-
dustry Organization, a Washington, D.C.-based trade group.
The market has grown by 16 percent each year since, peaking in 1996, when consumers spent $4.2billion on the top 10 biotech drugs. None is the transgenic sort PPL Therapeutics makes.
PPL Therapeutics raises transgenic cows, pigs and rabbits, whose genes have been mixed with another species' DNA so that their milk will have proteins that can be used in the production of drugs. The proteins are used to fight diseases such as emphysema and cystic fibrosis
For PPL, the end of the production line is the birth of a transgenic calf designed to produce therapeutic proteins in its milk.
Now, 7percent to 10percent of all live cows born at the company's 700-acre farm in Montgomery County have DNA that has been altered for that purpose. Those are grown to maturity, milked and mated. It's sort of a high-tech genetic crapshoot.
But when and if the cloning process is perfected with cows, the company can simply genetically copy the ones with the desired DNA.
In other words, every one that rolls off its production line will be a keeper.
The odds that Blacksburg's PPL will clone a cow are pretty high. The Scottish group that accomplished the cloned sheep, the Roslin Institute, is trying to patent the process. The Roslin group is negotiating an agreement that would license the process to PPL Therapeutics, Plc, the Scottish parent of Blacksburg's company.
|--| But that's all a down-the-road benefit. Work being done in 7,000-square-foot offices in Research Building 7 of the Virginia Tech Corporate Research Center actually contributed very little to the paradigm-shattering accomplishments on the sheep in Scotland. The Blacksburg folks are dealing with cows, rabbits and pigs.
Still, businesswise, you can't beat the residual publicity.
"We've been surprised at the amount of attention," said Julian Cooper, PPL's general manager. "It's not every day something you do gets the president talking."
Cooper was referring to the ethical ramifications brought by the news that a mammal had been cloned. After the announcement about the cloned sheep and the revelation a few days later that two monkeys had been cloned in the U.S., President Clinton banned federal funding for research on human cloning, which doesn't directly affect PPL in Blacksburg.
Cooper said his staff is learning the soon-to-be patented technology used on sheep and trying to apply it to cows in Blacksburg. They use cows because they're more like sheep than pigs are, and they make lots of milk.
Cooper said he's not sure when they'll clone a cow. A clone is a strain of cells descended from a single cell. They're still trying to find the right type of cell to use. Once that's chosen, they'll follow a process similar to that used to clone the sheep, Dolly.
The changes in a cloned animal are imperceptible, said Will Eyestone, head of bovine technology for PPL in Blacksburg. He said altering one DNA strand in one connective tissue cell of one 1,200-pound cow is as insignificant, relatively, as taking two names out of the Washington, D.C., phone book.
It's not enough of a change to noticeably affect the animal, but it's enough to cause a cow to make milk with human-like proteins.
Using human-like proteins in sheep milk, the 10-year-old Scottish PPL has made a drug called Alpha-1-antitrypsin. Trypsins chew up proteins. Anti-trypsins stop trypsins.
The British version of the Food and Drug Administration began testing the drug late last year. The testing process has three phases, and the agency is nearing end of the first.
The anti-trypsin drug is designed for use on cystic fibrosis patients, whose lungs are prone to infection. White blood cells typically kill off that infection. But that produces something that eventually starts to chew the lungs, making the patient more susceptible to infection. This drug blocks that cycle.
|--| Here's how transgenic animals are now made.
First, scientists decide which gene to use. Then it's grown in the lab and injected into a fertilized cow egg. A joystick-controlled glass needle, finer than a human hair at its tip, is used.
Sounds simple enough, but the process is intricate. Cell nuclei are fragile things, and an ultrathin glass needle, no matter how thin, can damage a cell if not used correctly. It takes lots of practice, Cooper said.
If it's all done right, the new DNA becomes part of the cell's DNA. Researchers don't know until the calf is born - nine to 10 months later - if their work was successful. Of those born, only 7 percent to 10 percent come out as desired - for now.
The cloning process currently is also inefficient. To get one live lamb, 277 sheep ova had to be discarded.
Once the cloning process is perfected, the genetic manipulation will be done and confirmed in the lab, rather than having to wait 9 to 10 months until the animal is born to find out.
With either process, the one used now or cloning, the embryo still has to be placed into the reproductive tract of the recipient animal - in Blacksburg's case, a cow. The process, similar to artificial insemination, doesn't require surgery.
Once the calf is born, a blood sample is taken to make sure the DNA is in the animal's cells. And once that's verified, the human-like DNA-bearing cows are grown to maturity, mated and milked. The milk is analyzed for the protein that the DNA was intended to produce. Then it's shipped to PPL's pharmaceutical company customers.
PPL in Blacksburg doesn't have a product yet. The company is working with pharmaceutical companies to develop cows with the proper DNA. It is still several years away from turning them into four-legged therapeutic protein factories.
|--| PPL Therapeutics Inc. grew out of a 1993 merger between a then-6-year-old Scottish company, PPL Therapeutics Plc., and Transpharm, a company started by Tracy Wilkins, director of Virginia Tech's Fralin Biotechnology Center.
They knew of Wilkins in Scotland because the industry was and is fairly small. Transpharm was created to commercialize Tech's transgenic technology expertise and some of its patent applications.
The merger was a natural: PPL worked with sheep but wanted the pig technology, which Transpharm had.
Also, PPL wanted to get into cows, and rural Southwest Virginia seemed like the ideal place: It's in the United States, which is not believed to have mad-cow disease, and it has Virginia Tech. Also, unlike Europe, Southwest Virginia has lots of space, which makes keeping cows less expensive.
That is what brought PPL here. It has stayed because of Tech's research knowledge and people. And also because of the Corporate Research Center.
"This is a very good facility," Cooper said. "They work very hard to help new and growing companies do well and survive. It's reasonably cheap, good quality accommodations. They work with you in many ways to help make life easier."
Joe Meredith, the Corporate Research Center's president, said PPL Therapeutics probably has received the most attention of any of the center's 55 private companies. He said he hopes PPL, with it's newly found international attention, sticks around.
"There is this perception that companies are here long enough to be successful, then they go off and do their thing, but that's not the reality," he said. "We want the companies to stay here forever, and hopefully we're doing a good enough job meeting their needs that they'll want to stay here."
LENGTH: Long : 167 lines ILLUSTRATION: PHOTO: Alan Kim. 1. Bovine eggs are invitro-fertilized the dayby CNBthey are delivered to PPL Therapeutics. The following day,
transgenes are injected into the pronucleus of the egg (shown on the
monitor) by Kerry Kendrick, a research associate at PPL and a
Virginia Tech graduate student from Fairfax. 2. Seven days after the
process begins, Will Eyestone, head of bovine technology with PPL
Therapeutics, examines and selects the cultured eggs that will be
transferred to recipient cows. color. Graphc: Chart by KRT. color.