Chemists exist between two extremes when it comes to research. On the one end there is the age-old method of trial-and-error. On the other is quantum mechanics. The former was the only available method for centuries. The latter works great — in theory.

But in the middle is the real world. This is where centuries of trial and error — much of which never aimed for anything specific, but rather was conducted just to see what happens when two substances collide — and recent advances in academics and technology intermingle. Scientists working on compounds today, whether for drugs or new materials or cosmetics, draw on all those things other scientists wrote down from their trial-and-error experiments and apply the facts to new computational models. And as computer technology advances, so does chemists’ ability to study the intricacies of molecular bonds.

John Kulp finds this approach to be most practical. A longtime high-tech entrepreneur and scientist, Kulp is one of the founders of Bio Leap, a Pennington-based firm that develops intellectual property on behalf of companies looking to develop pharmaceutical and other compounds.

Bio Leap does not develop drugs. It uses, among other methods, advanced computer models to discover how compounds for drugs and other materials will work together. For its pharmaceutical clients, Bio Leap works on the issue before it goes to clinical trial. The company usually gets a compound “when somebody says ‘we can develop this into a drug,’” Kulp says.

Bio Leap has two other locations — Cambridge, Massachusetts, where the company’s software development takes place, and Raleigh-Durham, North Carolina, where “the chemistry guys are.” In addition to working with pharma companies Bio Leap works with agrichemical, petrochemical, and cosmetic companies.

In Pennington, the company’s headquarters, there are six employees and no labs. Kulp, Bio Leap’s chief technology officer, oversees much of the computer-assisted work done here, which factors the innocent-sounding, yet highly technical concept of “stickiness” in molecular bonds.

The success or failure of a bond, Kulp says, relies on a molecule’s ability to stick to a protein. In general, the stronger and more stable the bond, the more effective a compound will be. But while that sounds straightforward, strong bonds can cause problems. The tricky part is creating strong, stable bonds in the right places amid a riot of molecules.

Creating too strong a bond between molecules might pull one of them out of place, which could negate its effectiveness. Or it might be too big a bond for the purpose needed. Bio Leap, Kulp says, prefers finding ways to strengthen weaker bonds (rather than altering too-strong bonds) because it gives scientists more control over the bond’s ultimate strength.

Computer modeling allows Bio Leap to do its research through a sort of virtual trial-and-error (what Kulp refers to as “guided guesswork”). This is necessary, says Bill Chiang, Bio Leap’s project management director, because the company does not have the luxury of time like an in-house pharma development team might.

“We still have to show people it works,” Chiang says, “but we’ve got to get this stuff out the door.” Companies developing compounds, he says, need go through the paces quickly, and Bio Leap’s cutting-edge software allows it to test and re-test compounds rapidly.

Bio Leap makes part of its money through licensing agreements and part by getting paid to solve problems with a substance’s development. “We get something they get stuck on,” Chiang says of Bio Leap’s clients. “They put up the money for validation. If it’s successful, we get a milestone bonus or maybe share the intellectual property.”

Chiang says that Bio Leap helps companies identify the intellectual property inherent in a substance. No one owns proteins or molecules, but companies do own the knowledge about how they work together in specific compounds. “We give them chemistries and novel ideas they might not have come up with on their own,” Chiang says.

Once you get a compound that works, it’s a matter of refinement. Kulp says a good chemist will know what and where he can substitute and modify. This does not mean, of course, that the path of discovery is always smooth, nor even always welcomed. Particularly in big, multi-tiered industries like pharma, Kulp says, giant leaps in innovation are often resisted because the results can alter too much too soon in the way a company does business. Often, this is the result of entrenched corporate culture, which developed one way and is now resistant to anything that challenges the status quo.

Kulp has a long history in technology. Born and raised in New Jersey, his father was a Columbia University professor who worked on the Manhattan Project. He earned his Ph.D. at MIT in electrical science in 1978. He stayed after he graduated, founding Symbiotics, which sought to develop artificial intelligence. “We were pretty esoteric,” Kulp says.

The company, he says, was founded in part as a countermeasure to growing American fears in the 1980s that Japan was poised to take over the world — particularly in the technology arena. The science Symbiotics developed, through its hardware and software, “achieved a technology pinnacle,” but had one major drawback — “it wasn’t what the customers wanted,” he says.

At least not in most cases. But some of the technology Symbiotics developed was bought by major corporations and was responsible for getting Pixar (now part of Disney) off the ground.

After building company sales to the $100 million mark, Kulp went to work for music entertainment company EMI in the early 1990s.

Kulp came back to central New Jersey to work in the bio-electronic systems lab at Sarnoff Research (now SRI Sarnoff). Because of his experience building tech startup companies, Kulp became involved in some of Sarnoff’s spin-off companies, including Songbird Hearing, a North Brunswick-based maker of disposable hearing aids.

Kulp ran Sarnoff’s digital video projects before founding Bio Leap in 2004. He started the company because he wanted to work for himself, he says.

As for the future, Kulp says Bio Leap is in a good spot geographically, at the heart of the northeast’s biotech industry. It also is in a good spot technologically because of the Internet. “The Internet has a profound effect on a company like ours,” he says. “The ability to bring together knowledge is just astoundingly different than it was even 10 years ago.”

#b#Bio Leap#/b#, 238 West Delaware Avenue, Pennington 08534; 973-761-6494. David Pompliano, CEO.

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