In the next few years, thousands of heart attack survivors may owe their lives to a woman who died nearly two decades ago from cancer.
A sample of her cancer cells, known as Bowes melanoma cells, were removed before she died and now grow in laboratories around the world. They're unique for one reason: They produce large amounts of tissue-type plasminogen activator, or tPA, a protein that may revolutionize the treatment of heart attacks.
Every animal body makes tPA, a protein that prevents clots from permanently damming up the flow of blood. Whenever a clot forms, nearby cells gradually release tPA, which sets in motion a complex set of chemical reactions to dissolve the clot.
But the body releases tPA too slowly to dissolve a clot and prevent heart attack damage.If physicians had enough tPA, they could inject it to dissolve a heart-attack-causing clot.
Not enough could be isolated for experiments, however, until the early 1980s, when Dr. Desire Collen from the University of Leuven in Belgium discovered that Bowes' melanoma cells produced large amounts of the protein. Painstakingly, he began to purify enough tPA to test its clot-dissolving properties.
At that critical point, however, the new field of gene engineering had matured enough to make a decisive contribution: A team of scientists at Genentech Inc. of South San Francisco, America's first biotechnology company, isolated the gene that produces the tPA protein.
Using Collen's tPA protein, the Genentech team created a probe to find and isolate the gene -- a chemical structure that encodes the information a cell needs construct a protein -- for tPA. That gene was then used to transform culture cells into chemical factories that can make virtually unlimited amounts of the protein.
If tPA receives Food and Drug Administration approval for widespread use, it could become one of Genentech's most important, and profitable, products.
"We can estimate a market size, by the fourth year of marketing, will be about $300 million dollars in the U.S. alone," says Genentech spokeswoman Susan Atkins. Genentech has formed partnerships with companies in Japan and Germany.
"The cost of tPA will be determined over time," says Gary Steele, Genentech's vice president of product development. "We are in no position to give the answer to that."
How long before tPA is available to heart attack victims is unclear. Genentech president Robert A. Swanson says the company will not file for FDA approval until the end of this year or the begininng of 1986.
And when it does reach the market, tPA may have some competition hot on its heels. Yet another clot-specific plasminogen activator called pro-urokinase was identified a few years ago by Dr. Victor Gurewich from Tufts University School of Medicine and St. Elizabeth's Hospital in Boston.
Pro-urokinase differs slightly from tPA, although both bind to clots and dissolve them. Whether it will prove to be better than tPA is unknown. Tests in people may begin sometime this year.
Pro-urokinase has one theoretical advantage, Gurewich says: It's more stable in the blood, so less would have to be injected to dissolve the clot. So stopping a heart attack with pro-urokinase could cost less than with tPA.