By Andrea Frazeur

Albert Lea, Minn. -- Natural Biologics, LLC isn't horsing around. It's stepping up, ready to challenge a pharmaceutical giant in the world of estrogen treatment.

The Albert Lea company has begun producing natural conjugated estrogen, the hormone many medical experts consider a wonder drug for aging women. Conjugated estrogen is derived from the urine of pregnant mares.

For more than 40 years, Wyeth-Ayerst, a division of American Home Products, has controlled the $1.2 billion U.S. estrogen market through its drug Premarin, the only source of conjugated estrogen. Natural Biologics is challenging that monopoly by providing the raw materials to make a generic version of Premarin.

"We knew the demand for the drug would be growing dramatically," says Natural Biologics Vice President Steve Saveraid. "There was room for a new entrant, plus a generic market."

Estrogen brief
In the 1940s, scientists discovered estrogen extracted from pregnant mares helped relieve the symptoms of menopause. Saveraid says industry leaders worked with horse urine because the horse is a large, arid animal that produces a gallon of naturally concentrated urine every day.

Although conjugated estrogen was originally developed by American scientists, the pregnant mare urine, or PMU, industry moved out of the United States and into Canada in the 1960s. Canadian regulations were more lax on hazardous chemical use in the extraction process and on waste disposal. Canada's cool temperatures also make it easier to handle PMU.

Under Food and Drug Admin-istration rules, companies may develop generic medications 15 years after the original drug is patented. To date, however, no U.S. company has broken into the Premarin market. None have figured out the trade secrets of the extraction process.

Scientists have also been unable to replace natural conjugated estrogen with a synthetic estrogen that qualifies. Natural estrogen contains 10 estrogen elements that must be combined together in a specific molecular structure.

Horses in the blood
The Saveraid family raises draft horses in Huxley, Iowa and Cushing, Minn. About 13 years ago, Steve's father Ken and brother David began leasing pregnant mares to urine collectors. Horses bred in summer were moved to Canada for six winter months, where the collectors cared for them in exchange for urine. The mares came home two months before giving birth in the spring.

In 1990, Ken urged his sons, who both have degrees in animal science, to look at the potential market for conjugated estrogen. They soon met up with Bill Stoll, then manager of AURI's Waseca office.

"I like projects that are a little off the beaten track," Stoll says from his St. Paul office, where he now serves as AURI's food scientist. "Here we were looking at a high-value raw pharmaceutical material not otherwise harvested here."

The Saveraids asked AURI to help them figure out the extraction process. Soon the AURI laboratory in Marshall was awash in gallons of PMU.

"We were not highly looked upon while doing the extraction. It was rather odoriferous," says Max Norris, AURI oils and fats scientist, "but we did get to the end of the hunt."

"In the early days AURI was key," says Steve, noting AURI provided the initial funding to test the process. "I'm quite certain it's why we are located in Minnesota."

Just in time
The AURI lab provided the Saveraids with 300 to 400 grams of bulk material that they used to obtain FDA approval. From those beginnings, the Saveraids went on to more in-depth investigations at the Hormel Meat Institute in Austin, Minn.

As early as 1994, company timelines dictated a plant operational by October 1997, and that's exactly what happened. They had broken ground just three months earlier.

"We were under extreme pressure to get this done by October 1, when the urine came. If you missed a season, you missed a year's worth of production," Steve says. "We had 50 people working around the clock on that plant."

At the same time, Natural Biologics was lining up 12 Minnesota farmers and 23 other Midwest farmers in six more states to collect PMU. Each farmer houses at least 50 mares, and Natural Biologics plans to eventually contract with a total of 100 producers.

Individual facilities can cost from $150,000 to $200,000, yet farmers can gross from $1,200 to $1,800 per mare. During the 1997-98 PMU collection season, Natural Biologics paid nearly $3 million to farmers.

Pampering pregnant mares
Taking good care of the horses is paramount to the Saveraids. About 85 percent are brought in from other farms during the winter months, when horses are generally kept indoors, and cared for in exchange for the urine.

"They are well cared for," Steve says. "We have a very strict code of practices."

Horse gestation takes 11 months. Mares in their fourth month are put "on-line" in October and urine is collected daily until March, two months before foaling. Mares of all types are used, but draft horses are most common because they have quiet temperaments and tend to be the most profitable producers.

Contracting farmers must insulate barn walls and ceilings and keep temps at 55 degrees. Barns have concrete floors, natural lighting and stainless steel stalls big enough for the mare to turn around and lay down in.

A soft rubber collection cup hangs underneath the horse, suspended by surgical tubing on a pulley system. "The (horses) don't usually leave the stall," Steve says, "but the truth is they could walk down the alley 15 to 20 feet. This tubing is really stretchy."

The tubing carries urine to a plastic container at the front of the stall. Urine is refrigerated in a bulk tank and shipped every four days to Albert Lea.

Saveraid says the mares have little difficulty getting used to the collection device. They are exercised regularly, given well-balanced rations and plenty of fresh water. "This is agriculture, we won't deny that," he says, "but as far as care of these horses, this is really quite good."

Going to town
As an FDA-registered GMP facility, Natural Biologics can manufacture and sell conjugated estrogen. The next step is for pharmaceutical companies to develop the raw material into a treatment and conduct testing for generic FDA drug approval. Steve expects the process will take 10 to 15 months.

Currently, Natural Biologics has 25 employees and is stock-piling estrogen so they have enough when a generic drug is approved.

Albert Lea city officials are happy Natural Biologics decided to build in their town. "This plant has brought in highly technical jobs in chemistry and biology. We haven't been able to pull in people like this in the past," says Paul Sparks, city manager. "This process is very high tech."

Health care effects
As baby boomers make their way through their forties and fifties, conjugated estrogen is getting more publicity. By the year 2000, 50 million menopausal women in the United States will be candidates for estrogen therapy, supporting a projected $3 billion industry.

Estrogen replacement therapy is often recommended for women at risk for heart disease or osteoporosis. New studies also suggest estrogen maintains mental ability and slows down the onset of Alzheimer's disease.

"I think the biggest change in the estrogen market is the realization that many women need to take it the rest of their lives after menopause," says Steve. "This is probably the lowest cost treatment, one that affects health care in many different ways."