Biological Disaster

Zonagen Inc. took its name from Bonnie Dunbar's groundbreaking research into contraceptive vaccines. Then, when she wasn't looking, the company took her research.

As its name suggests, Zonagen was, from its birth, inextricably linked to Bonnie Dunbar. Since the 1970s, Dunbar's research has focused on isolating certain proteins from the zona pellucida, the protective shell around the ovarian egg, that elicit an antibody response that prohibits conception.

And as Bonnie Dunbar's career suggests, no one else has come as close to developing a contraceptive that's as easy to use as getting a flu shot.

"Other scientists are doing this kind of work, of course," says Debra Wolgemuth, a New York molecular biologist and occasional research collaborator with Dunbar. "But there's simply no question that Bonnie is a true leader in that field, and has been for some time."

The daughter of a wheat farmer and a schoolteacher, Dunbar was raised in Colorado on ancestral land settled in 1862. An enthusiastic competitor in science fairs as far back as junior high school, she became hooked on reproductive science at the University of Colorado, after a classroom showing of the documentary Birth of the Red Kangaroo. At Colorado, Dunbar earned a master's degree in zoology, then began her doctorate work at the Institute for Molecular and Cellular Evolution at the University of Miami Medical School, where she began her work on contraception by studying ways to neutralize the male sperm.

Dunbar later followed a mentor to the University of Tennessee, where, in 1977, her research took a critical turn when she discovered that one cause of infertility in women is an antibody attack on the zona pellucida. Her research was so novel it ended up on the cover of Science magazine.

For postdoctoral research at the University of California at Davis, Dunbar collected the raw material for her zona pellucida studies by driving 90 miles to a slaughterhouse, where she donned a hardhat and, for hours at a time, went from one pig carcass to another, collecting ovaries. It was the only way she could accumulate enough protein to conduct biochemical research on the zona pellucida.

"I had no money, and my department wouldn't pay for me to get this stuff any other way," she says. "It wasn't a pleasant job. I guess you could say that's where I paid my dues."

In 1978, Dunbar was hired by the Population Council of Rockefeller University in New York to begin work on a nonabortive, human contraceptive vaccine using animal models. The council had enough money to keep Dunbar out of the slaughterhouses, but there was still the matter of extracting the zona pellucida from the ovaries, a messy, time-consuming process. To simplify the task, she developed a machine that carefully sliced open the pig ovaries, then sifted through the millions of immature eggs, called oocytes, to separate them from the protein.

While in New York, Dunbar received the first of several grants from the National Institutes of Health and began injecting soluble zona pellucida into female mammals. That research led to the discovery that pig zona pellucida, when injected into rabbits, would bind to the rabbit's zona pellucida and create a kind of biological condom that would prevent sperm from fertilizing the egg.

"This was really the basis for the animal contraceptive vaccine," Dunbar says. "In every case, the rabbit ovaries shrunk up and there were no more oocytes. It was essentially the exact same thing as spaying. The animal became sterilized."

In 1981, as Dunbar was preparing to join the faculty of Baylor College of Medicine, a breakthrough in genetic engineering called "lambda gt11 library screening" gave researchers the ability to identify genetic information from a very small amount of protein. That meant Dunbar no longer needed to visit slaughterhouses or employ a machine to isolate zona pellucida proteins. She could now clone them -- which ensured that large enough quantities could be produced for commercial use.

As it happened, Baylor's cell biology department, chaired by National Academy of Sciences member Bert O'Malley, was on the cutting edge of genetic engineering by the time Dunbar arrived in November 1991. Suddenly, what once took Dunbar six years to accomplish -- the harvesting of sufficient zona pellucida proteins -- could be done in two days.

"In theory," she says, "you could make enough contraceptive vaccine to immunize the world in about a week."

While Dunbar was making strides toward a contraceptive vaccine, iconoclastic oilman George Mitchell, who built The Woodlands, was looking for ways to counteract the sharp downturn in oil prices. In 1983, he formed The Woodlands Venture Capital Company to back start-up companies involved in biotechnological and health-care services. By the following year, Congress had enacted a series of laws that encouraged the transfer of research from federal laboratories and state-owned universities to the private sector, while giving businesses the means to protect their investments through exclusive licensing and royalty agreements.

By the late 1980s, Mitchell's investment firm had taken advantage of the new laws, as well as the easy proximity to Texas Medical Center, to start a half-dozen companies. The first alliance with Baylor was Amnion, Inc., a high-tech holding company formed in cooperation with BCM Technologies, Baylor's for-profit technology-transfer subsidiary. Amnion was eventually bought by Cobe Laboratories of Lakewood, Colorado, for $12.6 million. Baylor received $1.5 million from the buyout.

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