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Scientist Drawn By Mad Cow Mystery

Posted on: Monday, 9 February 2004, 06:00 CST

Some 12 years may pass before the unluckiest ones discover that in 2003 they consumed American beef infected with a disease called "mad cow."

If they show the symptoms - they will stumble and stagger, their speech will slur - then within six months they will almost certainly die.

Dr. Charles Weissmann knows this. But the world-class scientist who will direct The Scripps Research Institute's Florida expansion also understands something else: Finding a drug to stop this disease is not only plausible, it is possible within his lifetime, possible within theirs. And it may just happen at Scripps' Florida campus.

At a time when most men prefer to retire, Weissmann, 72, has one more major discovery to make. In pursuit of it, he intends to dismantle his laboratory at University College in London - a lab that has played a key role in responding to Britain's mad cow epidemic - and move much of it to what now is wetlands and orange groves in northern Palm Beach County.

What drives him are the lingering mysteries of this protein- based disease, and a sense that he must move quickly.

Scripps has the technology and resources to do that, he said in a series of e-mail exchanges and interviews from London.

"In collaboration with other scientific groups, I'll have a shot at it," Weissmann said.

How soon?

"Ten years is probably a good bet."

Weissmann is a tall, imposing man with a dignified demeanor, a pointed wit and a love of art, cinema and music. In the company of fellow scientists, he erupts with puns and clever repartee. But after a lifetime of being occasionally judged, misunderstood and misquoted, he speaks cautiously around nonscientists.

Like an Ayn Rand character, he is a captain of both industry and science. He has cloned interferon, helped found the billion-dollar biotech firm Biogen, served on the boards of numerous business and scientific groups including pharmaceutical giant Hoffmann-La Roche, and contributed to the basic understanding of prions, misshapen proteins that cause disease, distinct from viruses and bacteria.

Science is his passion

He has mentored countless important scientists, said his friend and collaborating scientist Dr. Adriano Aguzzi at the University Hospital Zurich in Switzerland.

"He is the smartest scientist I have ever met, and I have met a lot of them," Aguzzi said. "He thinks so quickly it's unbelievable."

Aguzzi believes that the Nobel Prize awarded to Stanley Prusiner in 1997 for identifying the prion as a cause of disease could easily have been shared by Weissmann.

"Stanley Prusiner was really fighting a battle - fighting for recognition of the prion as the agent of disease, and Charles Weissmann really set out the real scientific grounds for this argument. I think that without Charles Weissmann there would have been no chance for Stanley Prusiner to win the Nobel Prize. No chance."

Weissmann shrugs off the question of the Nobel. He likewise dismisses suggestions that he is coming to Florida because of the research money - "I have never lacked research money."

Weissmann's wife, Juliette, in an interview from Zurich, described her husband as a man consumed by his work.

"His real love, his real love is science," she said.

The two met when she was 17 and he 26, a meeting arranged by family members who thought they would make a good match. Romance bloomed, but "he thought I would not be happy to have a husband who would work so much," she said.

"At the end, perhaps he was right."

The two eventually married others, and each had three children. A chance meeting 10 years later led to what she calls "a terrible love story - terrible because so many children were involved."

There was an affair, divorces and finally, 23 years ago, a new marriage. By then, Juliette was a fashion designer and owned an art gallery in Zurich. Her husband credits her with kindling his own interest in art. Now he collects the works of Rene Magritte, Francis Bacon and Jean-Michel Basquiat.

He loves classical music - Igor Stravinsky and Claude Debussy. He loves movies. He skis in the Swiss Alps, where he spent most of his childhood.

During World War II, his father, a film distributor, kept their Jewish family in Rio de Janeiro, out of fear of a Nazi invasion. The invasion never came, but Weissmann attended Portuguese-language schools and developed a taste for international travel and adventure and a facility with languages. He speaks English, German, French and Portuguese fluently and is comfortable with Italian and some Spanish.

"He has incredible drive and capacity to work," Juliette said. "In London, he leaves the house at half past 8 and comes home at half past 9, and he still works almost until midnight at the computer."

Sense of urgency

Nowadays, his late nights involve planning the new Scripps base in Florida. And pursuing his passion - prying into the lingering mysteries of prions.

A technology called high throughput screening may provide the quickest path to a prion therapy, Weissmann said. Scripps has that technology and a library of chemicals to draw from. His London laboratory does not.

The screening tool robotically tries to fit one molecule after another into a protein receptor - like a burglar testing thousands of keys in a single lock, hoping to break in. Finding the proper keys to test is part of the challenge.

This is no small task.

Research suggests that, in their healthy form, prion proteins sit on the surface of healthy nerve cells and might play a role in their survival.

But when a diseased prion contacts a healthy prion, it appears that a chain reaction ensues. The healthy prion protein assumes the abnormal shape of the diseased one. Then the healthy nerve cell self- destructs. The reaction spreads, ultimately causing death.

From the mad cow epidemic in England, scientists know that millions of people may have been exposed to diseased beef, yet only about 150 are yet known to have sickened and died. The average incubation period is a little more than 12 years.

There is a sense of urgency to learning how many more people may become sick and why others don't appear to be ill, said Dr. Anthony Williamson, a researcher at Scripps' main campus in La Jolla, Calif. "There's no diagnostic tool other than to look at their brain after they die," he said.

Williamson's team has suggested that antibodies have the power to fight prions. The trick is to find the elusive molecular key enabling antibodies to neutralize harmful prions. Scripps' ability to test out those keys quickly will save countless hours, Weissmann said.

It's even harder than it sounds.

"There is no rational way of designing a drug, despite what many biotech companies say," Weissmann said. "It's still luck. You can make an informed guess, but the bottom line is you have to test hundreds of thousands of compounds until you find one that has some effect. Ten years ago, you could test a few hundred per month. Now you can test 100,000 per week."

To find the key would be the crowning achievement of a 50-year career that has already made history - and fortunes.

Interferon pioneer

In 1979, Weissmann beat biotech pioneer Genentech by three weeks in announcing the synthesis of genetically engineered interferon.

The announcement - controversial in scientific circles because it was made in a press conference rather than through a scientific journal - kicked off a biotech frenzy that sizzled and then fizzled on Wall Street in the 1980s.

Two years earlier, Weissmann had bucked scientific convention by linking his university work to business.

A venture capitalist named Raymond Schaefer recruited him and other noted European scientists to form the company that is now Biogen Idec.

It led to "unpleasantness" with colleagues, recalls Weissmann's wife, Juliette.

"They did not believe it was good to have scientists in business," she said. "Now everyone wants to do it, of course."

The company's first successful product was interferon, a substance produced in tiny amounts by cells under viral attack. It seems to alert nearby cells to the attack and provoke them to protect themselves.

Early on, there were high hopes that it could treat everything from the common cold to cancer. Today, forms of interferon are used to treat hepatitis C and multiple sclerosis, although it proved to have too many side effects to treat many other illnesses. In a memoir about the 20th anniversary of the cloning of interferon, Weissmann recalled those heady days:

"Our lab was flooded with requests for interferon, often in the form of desperate letters, all of which I answered in an appropriately apologetic fashion. A seemingly endless stream of reporters requested interviews and information, and feeling guilty of having initiated the publicity, I felt obligated to clarify and explain the cloning of interferon to one and all."

The Scripps campus in Florida is intended to push basic research toward the marketplace, too. But Weissmann said the scientists he recruits will be free to collaborate with others outside Scripps.

"I will encourage an open policy on publication, requiring only that scientists submit an early draft of their report to the institute in order to allow a patent application to be prepared if appropriate," he said.

He is recruiting his research team now, Weissmann said. Once it's in place, he plans to work side by side with them, testing and retesting hypotheses, relentlessly questioning.

At least for now, retirement is not an option.

"I want to find the answers to my questions," he said. "Maybe God is going to retire me. Who knows?"

stacey_singer@pbpost.com

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