The Little Piggy

When last we spied reproductive physiologist Doug Greger, in the January 1997 issue of Research/Penn State, he was standing on a white-sand beach in Vanuatu, a tiny island republic in the South Pacific Ocean, gazing out to sea.

pig next to fence

Pigs had carried Greger to that distant corner of paradise. Intersex pigs, to be exact: A dwindling population of genetically male porkers who, because of a glitch in their hormonal development, were insufficiently exposed to testosterone and so had ended up with female, as well as male, sex organs.

On Vanuatu, these hermaphrodites, known as Naravé pigs, have been prized for centuries, serving as both religious objects and measures of wealth. To Greger, a doctoral student in dairy and animal science, they represented a fresh chance to solve the boar-taint problem.

Male pigs produce in the testes a steroid called androstenone, a precursor of the pheromone called androstenol. Released in their saliva, androstenol is the secret weapon that makes porcine Romeos irresistible. (Humans like the smell, too: Something close to androstenol is present in musk-type perfumes.)

But some things are best in moderation. Androstenone is also stored in a male pig's fat, and in this form, the steroid gives off not a pleasant musk but what Greger calls a "foul, urine, sweaty odor," particularly when the fat is heated. In other words, the meat of the male pig, cooked, has a less-than-appetizing smell. Boar taint.

The pork industry's solution is to stop the hormonal cascade at its headwaters—by removing the testes. "Virtually all male pigs destined for meat production are castrated," Greger says, "usually within the first four or five weeks of life." But castrated males—barrows—produce fattier meat than boars do, and require more feed to make weight. Altogether, Greger estimates, castrating costs about 10 percent of pork production efficiency. Seeking a less drastic way to prevent androstenol's production, Greger decided to look more closely at how the hormone is made.

The synthesis of steroids requires many steps, each one regulated by enzymes. The quickest way to make sense of this particular enzyme pathway, Greger reasoned, was to find a pig in whom it wasn't working, and then see which step was missing. Locating an untainted boar, Greger quickly realized, might require screening thousands of animals, and finding that many intact males would be next to impossible. But the same enzymes that produce androstenol also produce testosterone. And a defect in the testosterone pathway, he knew, would be easy to spot: it would result in an intersex pig.

Greger had read about the pigs of Vanuatu in a British monograph published in 1928, and decided to see for himself. In three weeks on Vanuatu, he and a fellow adventurer, freelance zoologist James McIntyre, took blood samples from 19 Naravé pigs. When the blood was shipped to New Zealand for analysis, it showed evidence of a defect in an enzyme known as P450C17.

Greger picks up the story. "The gene for that enzyme is called CYP17. So I came home and started working on sequencing it. I had sequenced about 10 percent of the gene, at the part where I thought I would find a difference. And it was not different. It was identical to what you find in domestic pigs. And I didn't have the money to go any further."

Discouraged, he turned to finishing his dissertation. But not before filing for a patent on CYP17. "Basically I filed on my hypothesis of how I could change the gene so that it wouldn't produce androstenone."

Swine genetics companies, he soon found, were interested in his idea. By August of 1998, he was ready to sign a licensing agreement with one of them. "Right then the pork market took a nosedive," he says, "and the company got nervous."

Greger shopped the idea around, seeking the funding he needed to prove his hunch. "Then, in January '99, while I was trying to finish my thesis, I had a breakthrough. I realized I had been looking at the wrong gene. When I defended my dissertation in early April I told my committee: 'CYP17 may not it. There's another gene.'"

A week later Greger approached Ron Huss, then a technology licensing officer and now associate director of Penn State's Intellectual Property Office. He was pretty sure that the "other" gene was CYP11a1, he told Huss, but he needed a small grant to do the study that would prove it.

"I had categorized a group of 50 boars," Greger remembers. "High or low according to a biochemical measurement of boar taint. I wanted to compare the five high scorers to the five low, to see if there was a difference in this one area of this one particular gene."

pig lying down

Huss found the money through the Ben Franklin Partnership, a state-funded economic-development program. "So I did the work," Greger says. "I sequenced about 2,400 base pairs of the DNA from one section of CYP11a1. I compared the five high-taint boars to the five low, and found what's called a single-nucelotide polymorphism—a change in one base-pair. Four of the five high-taint boars had it, and none of the five lows did." From that group of ten, Greger was able to develop a test that allowed him to quickly and accurately identify animals that have the crucial change.

"I made the discovery in May," Greger remembers. "I had already committed to go to the University of California at Davis to do post-graduate work." So, after filing patents on his test and on the appropriate sequence of CYP11a1, he left for California.

Meanwhile Huss and Tom Monahan, director of Penn State's IPO, started shopping around for a company that would buy the rights to this technology.

But Monahan was also, at the time, exploring new approaches to marketing intellectual property. With funding from Ben Franklin, he had hired Tim Murphy, a new-product specialist with an M.B.A. from Harvard, to look at alternatives to standard licensing, including start-up ventures. What if, instead of selling off the rights to an idea, the University could attract investors willing to start a brand-new company to develop it? Instead of royalties, the University would retain part ownership of the company.

Similar arrangements had worked at other universities. "The potential was here," Monahan says. The best approach, the most attractive to investors, would be to bundle several technologies as a package and form a company to commercialize all of them, reducing the risk in case one idea failed. So Murphy, Monahan says, "went prospecting—analyzing our existing invention disclosures for the ones that looked like the best opportunities." Murphy focused on agriculture and advanced materials—two of Penn State's recognized strengths. Out of the agriculture pile popped three inventions, all of which he considered strong, that seemed to fit well together.

The first, an idea of Regina Vasilatos-Younken, professor of poultry science, is a nutritive supplement for feeding chickens just before slaughter that reduces the risk of microbially contaminated meat. The second, patented by Daniel Deaver, professor of reproductive physiology, is a gel drug-delivery system that could improve fertility rates in cows and other farm animals. The third is Greger's genetic marker for boar taint.

Murphy found a principal investor in Frank Slattery, who had successfully started companies based on technologies developed at Princeton and Penn. He found a skilled and experienced manager, fellow Harvard-M.B.A. Joseph Duffey. Greger was persuaded to return from California. Finally, in September 1999, the deal was struck and EIEICO, Inc. (as in the song "Old MacDonald") was born, with Slattery as chairman of the board, Duffey as president and CEO, and Greger, who filed a total of eight patents as a graduate student, as Chief Technology Officer. In addition to being EIEICO's resident scientist, Greger heads his own subsidiary, Templar Sciences, to develop the boar-taint technology.

For Greger, sitting in his new office at EIEICO headquarters a mile from campus, it's what he was dreaming of on that beach in Vanuatu: the resources and opportunity to see his long-pursued solution all the way to market. "There's still a lot of work to be done," he says. "But this could turn out to be something big."

Douglas Leigh Greger, M.S., will receive his Ph.D. in dairy and animal science from the College of Agricultural Sciences in May 2001. He is currently Chief Technology Officer for EIEICO, Inc. and Templar Sciences, State College, PA. For more information on EIEICO, Inc., see http://www.eieico.com/.

Last Updated May 01, 2001