As vice president of a biochemical manufacturer, Joseph Toce helps supply other companies with the raw ingredients for drugs that combat AIDS, cancer and a host of other diseases. To get those ingredients, Toce turns to an unexpected source.

By Bonnie Gelbwasser

The building blocks of this industrial chemist's career aren't made of brick or concrete. Instead, they are the building blocks of DNA, the double-stranded molecule that contains the code of life.

Joseph Toce is a vice president of Reliable Biopharmaceutical Corp., a St. Louis-based bulk manufacturer of nucleic acids, biochemicals and enzymes for the pharmaceutical and biotechnology industries. The company is one of the world's largest producers of deoxynucleosides and deoxynucleotides, some of the components of DNA. It isolates them from salmon milt, the fish's sperm duct, which has proven a rich source of DNA.

A native of Hartford, Conn., Toce graduated from WPI in 1970 with a bachelor's degree in chemistry. He earned a doctorate in biochemistry at the University of Wisconsin, Madison, in 1979 and began his career at Sigma Chemical in St. Louis. He joined Reliable as director of research and development in 1984 and became a partner in 1989.

In March 1998, he was one of 68 honorees to receive the Tibbetts Award from the Small Business Innovative Research (SBIR) Program. The award is named for Roland Tibbetts, a longtime advocate of small business participation in government research who retired from the National Science Foundation in 1996. Toce was honored for "a cascade of developments his work has produced and for furthering biotechnology and fostering high-tech business growth." Under Toce's leadership, Reliable won a total of seven SBIR Phase I and Phase II grants from the National Institutes of Health in 1989 and 1990.

The process of isolating DNA from salmon milt begins with salmon fisheries, primarily in the Pacific Northwest. Fishermen harvest the sperm ducts from sexually mature salmon, usually chum salmon (the most common variety), when the fish return to the area's waters to spawn. "The fisheries remove the whitish-pink milt, which resembles a large, flat hot dog or a piece of bologna, when they gut the salmon for meat or other uses," says Toce. "It is then flash-frozen and shipped to us.

"With assistance from the SBIR grants, we developed what I refer to as 'slop-bucket biochemistry,'" he explains. "The technique enables us to break the DNA down and then isolate the four basic building blocks from it. The milt is ground up, precipitated, digested and purified to produce the building blocks, which end up as a bunch of white powders that we sell as a commodity. It's like buying a chemical off the shelf. We process about 100,000 pounds of milt to get 1,000 kilos of nucleosides. Our capacity exceeds two million pounds of milt per year. The company is the only one in North America doing this type of work. All of our competition is in Japan."

Toce's work has led to major developments in the production of drugs for AIDS, cancer and other viral diseases, increased the size of Reliable's work force from 15 to 55, and generated millions of dollars in sales. In addition to Toce, the company currently employs three other Ph.D.s, plus 45 bachelor's- and master's-level chemists, and support staff.

In 1993 Reliable opened a new, technically sophisticated 51,000-square-foot manufacturing and biotechnology center on 4.8 acres. In addition to isolating DNA, it also offers producers ultrapure biochemicals, bulk pharmaceuticals and enzymes.

William Ash, Reliable's president and owner, founded the company as Reliable Chemical in 1968. It currently serves more than a dozen publicly traded NASDAQ companies, such as Isis Pharmaceuticals and Hybridon, which require large quantities of DNA building blocks to bring drugs to market.

The technique Toce developed allowed the company to commercialize the DNA building block production process and make it available to its customers at a much cheaper cost. "Biotechnology companies need significant quantities of materials," he says. "It takes a minimum of seven years and several hundred million dollars from the time a scientist comes up with an idea for a therapeutic drug until it's out. That's been a problem. Most of the drugs we and our customers are involved with are in clinical testing or preclinical testing situations. The things we deal with are years away from the market.

"This is a production facility," he adds. "We are in the business of making products, not discovering new drugs. We're a wholesale manufacturer. For example, in the AIDS drug AZT, we isolate the T. Other companies put the AZ on. We do not make the finished pharmaceutical tablets, but we do produce the active pharmaceutical ingredients (API) in bulk and under FDA inspection. These go to companies that make final finished pharmaceuticals and they do the formulations to the final dosage. It's really two separate processes.

"We are driven by what our customers tell us they need. Every day brings something new, though some projects are pretty mundane and straight up. We have expanded into a whole new area of nucleic acid-based chemistry. We're producing deoxynucleoside triphosphates used in polymerase chain reaction (PCR) for DNA fingerprinting and sequencing the human genome. Nuclei acid chemistry research has brought us new customers involved with genetic material--whether it's anticancer or viral drugs."