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is groundbreaking work in the area of immunopharmacotherapy -- specifically, an antibody that appears capable of neutralizing the effects of cocaine and the development of a chemical warfare detection kit -- put him in the spotlight twice in the last year.

In all fairness, the chemical warfare detection kit attracted attention in part because Janda wouldn't disclose the source of his funding to the media much beyond a tantalizing spy novel response: it came from an unnamed government agency, he said.

"Someone at this unnamed government agency asked us about a detection kit," Janda explains, "and said he would fund the project. We came up with the methodology, an on-site color kit. Basically, all chemical warfare agents are nerve gases -- sarin, soman and VX. All three decompose to a common element known as MPA (methylphosphonic acid) and our test detects MPA."

Janda and a colleague created a monoclonal antibody that could recognize MPA molecules after they'd been marked with a special chemical solution. It worked quickly and easily: If the antibodies recognized the decomposed remnants of sarin, the mixture changed color.

"The agency paid us to develop the technology but never did anything more with it," he adds. "This was before the Sudanese bombing, so they could have used our methodology there."

BREAKING AN ADDICTION

The cocaine antibody was a much different and much more significant discovery, both in terms of its science and its potential usefulness. It made the national news, appearing on both cable and network television and in all the major newspapers. That wasn't what impressed Janda, a man who takes his work seriously but admits to taking himself less so.

"I knew we'd made it when we got on the Tonight Show and Politically Incorrect," he jokes.

Janda, who received his Ph.D. in chemistry from the University of Arizona in 1984 and came directly to TSRI after that, clearly understands that cocaine addiction -- more psychological than physical but still difficult to treat -- is a serious problem in the United States. The National Institute on Drug Abuse and Alcoholism estimates that more than 2 million people need treatment for their dependence on cocaine. After that, the statistics turn even grimmer: Approximately 900,000 Americans start treatment but at least three-quarters of those return to using the drug.

"The media used the word vaccine to describe the antibody but that's a bit broad," he explains. "It's what we call active immunization because the antibodies are produced within the body. We created a specific polyclonal antibody immune response that attaches itself to the cocaine molecule and prevents it from reaching the brain. It's like painting a bull's eye on cocaine so the immune system can recognize and remove it -- the same way the immune system removes all foreign substances in the body. In layman's terms, a bunch of little antibody PacMen go around gobbling it up. It has to do it very rapidly because cocaine has a very short half-life in the body -- around twenty minutes or less."

Janda points out that they have created another version of the cocaine antibody that is so prolific it can actually draw the cocaine molecules out of the brain. This is the passive version because these cocaine-binding antibodies are first produced in the lab and then injected. The antibody acts like a giant sponge, soaking up the cocaine. Janda believes that the antibody's unique ability to rapidly neutralize large quantities of cocaine within the body could be extremely useful in emergency rooms where physicians must deal with critical overdose situations. Using a two-antibody therapy (passive and active), he adds, totally obliterates cocaine from the system.

While the effects of the active immunization antibodies now last for several months before a booster shot becomes necessary, Janda and his colleagues are working to create passive antibodies that will also last longer -- up to a month. With long lasting antibodies in place to continually block the drug's high, there is much smaller chance of a relapse, at least in theory.

THE HUMAN EQUATION

When Janda announced the possibility of human clinical trials later in the year, the public reaction to the story intensified substantially, adding a highly uncomfortable element to the whole media experience. His laboratory has been inundated with hundreds of emails, phone calls and letters from families, spouses and loved ones begging for his attention.

Janda emphasizes that the people who write him or try to make contact are desperate for help and see his work as their last chance. He can't help them but he understands their desperation. "I read some of the emails and they make very sad reading," he adds.

He also believes the antibody is a worthwhile treatment and a safe one. Once, while filming a segment of an English program called Tomorrow's World -- what Janda describes as the British version of 60 Minutes -- the interviewer asked him if he would be willing to give his vaccine to children. Yes, Janda said, he would -- it might help prevent the problem from ever getting started.

Even though Janda claims to enjoy interviews, it's clear that his recent media experience goes far beyond the normal life of a scientist.

"This is so much different than my regular work," he said. "My bread and butter is catalytic antibodies."

WHERE ORGANIC CHEMISTRY MEETS BIOLOGY

Janda's undergraduate work was in clinical chemistry, learning the techniques of a modern medical laboratory. However, his graduate work was in organic chemistry, the creation of molecules. His goal after graduate school was to find somewhere he could blend his knowledge of organic chemistry with biology. TSRI turned out to be the exact place he needed. Dr. Richard Lerner, currently president of the Institute, had just become head of the Department of Molecular Biology and was looking for young chemists to work on the idea of creating catalytic antibodies. Janda was one of the first chemists hired.It was a good match from the very start.

"I think the real advantage of Scripps is that there are no hard lines drawn for what you want to do," Janda says. "Doing good science is everything here, so you can cross over to any area you want. In a lot of places there are the old classical dividing lines between disciplines. Here there are a lot of undefined areas -- and the opportunities that go with them."

Janda describes the work of his lab as moving into areas that are interesting. For him, interesting cuts a fairly wide swath.

"In our lab we do everything from hardcore organic chemistry to molecular cloning techniques and polymers to immunopharmacotherapy and cancer," he says. "Several years ago we did some work with early HIV protease inhibitors, so our work with cocaine antibodies -- immunopharmacotherapy -- while important, is not our primary focus."

CATALYTIC ANTIBODY RESEARCH

The laboratory is focused on four major areas: catalytic antibodies, combinatorial chemistry, enzyme inhibition and immunopharmacotherapy. By using tools from other disciplines such as molecular biology, immunology, enzymology, and neuropharmacology, Janda and his colleagues work quite comfortably at the nexus of chemistry and biology.

At the moment, the best spot for that is, as he says, catalytic antibodies. The role of a catalyst in any chemical reaction is to accelerate that reaction. In the past, immunization -- the induced production of antibodies by the immune system to prevent a disease -- has relied exclusively on inert antigens -- basically dead substances such as the discarded protein shells of viruses. At TSRI, Janda's laboratory developed antigens that mimic part of a chemical reaction, allowing them to create catalytic antibodies that accelerate that reaction.

Add to that, the laboratory's development of a system that allows for the direct selection of a specific antibody function by using chemical selection from existing libraries of existing antibodies and the enormous potential of his work appears obvious.

Clearly part of that great potential is the laboratory's recent development of human antibodies capable of recognizing specific markers on certain tumor cells called glycopeptides. Although they are very rare, these antibodies are produced by cancer patients and are present in their bloodstream. By taking blood samples from these cancer patients, Janda and his colleagues have been able to reproduce these rare human antibodies that not only recognize tumors but also, in fact, seek them out.

"If we can produce these human antibodies in large enough quantities," Janda says, "we could attach them to specific drugs that destroy these tumors. It's a rifle shot approach to cancer therapy, one that should be significantly more effective than the traditional chemotherapeutic approach."

Although he claims he's not interested in producing compounds with commercial potential, he believes that his methodologies will help others produce them. What commercial aspirations he has he exercises by helping create new biotechnology start-up companies.

NEW BIOTECHNOLOGY COMPANIES

The first was CombiChem, a five-year-old California company involved in combinatorial chemistry. By accelerating the discovery process of leading drug candidates, CombiChem helps move viable lead candidates into the R&D pipeline more rapidly and with a greater chance of success. It was Janda's involvement with the development of the cocaine antibody that led to the founding of another start-up, Drug Abuse Sciences.

But like the sudden publicity surrounding the announcement of the cocaine antibody, starting a company was never his main goal. In truth, he seems almost to have stumbled onto the whole idea of medical commerce and appears bemused by the fact. But things have a way of moving in self-fulfilling circles.

Take his golf game, for instance.

FORE!

"I picked it up early and kept at it," he said. More than keep at it, he excelled at it, playing tournament games before he was six years old, winning numerous competitions in the state of Ohio. He played well into his college years, becoming one of the school's most prominent scholar-athletes.

He still plays but not often, perhaps once a month. He shoots between mid- to low-70s with no handicap. A good score recognized by anyone who knows the game, just as anyone familiar with the game would quickly recognize the name of chair Janda occupies at Scripps: The Ely R. Callaway Chair in Chemistry.

"Callaway Golf funds my chair in chemistry and it had something to do with my playing ability," Janda says. "Ely Callaway was interested in funding a chair at Scripps, so Richard Lerner said he knew an outstanding scientist who was also a scratch golfer. It more or less happened after that."

In the midst of all this serendipity, what holds Janda is the work. Most days -- most weekends, too -- you'll find him in the lab. Science, he says, knows no calendar and it remains at the center of his life.

"One of my mentors used to tell me that when chemistry isn't fun anymore, it's time to get out," he says. "Coming to work to me is still fun. There are a lot of things out there to find and discover. I'm still looking."