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The Dark Soul Of A New Drug


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THE DARK SOUL OF A NEW DRUG

THE BILLION-DOLLAR MOLECULE: ONE COMPANY'S QUEST FOR THE PERFECT DRUG

By Barry Werth

Simon & Schuster x 445pp x $25

In the biotechnology industry's frenzied hunt for new drugs, few stories are more compelling than that of Joshua Boger. The brilliant young chemist quit a top job at Merck & Co. in 1989, complaining that the world's most successful pharmaceutical corporation had grown too big and bureaucratic to develop new drugs rapidly. Even though he had a good chance someday to head Merck's research labs--one of the most prestigious posts in science--Boger left to start Vertex Pharmaceuticals Inc., vowing to redefine how drugs are made and to beat Merck at its own game.

The Billion-Dollar Molecule: One Company's Quest for the Perfect Drug is the inside story of Boger, Vertex, and the human drama surrounding the evolution of a promising young company. Barry Werth, a freelance writer, spent four years as a fly on the wall at Vertex and wound up with a riveting tale that has more in common with a John Grisham thriller than with dreary tomes on modern science. The book sheds light not just on Vertex but on the entire biotech industry and the competitive spirit that drives hundreds of small companies trying to develop new drugs.

The first goal Boger sets for Vertex is to create an improved version of an experimental drug that suppresses the immune system. The drug, discovered by Japan's Fujisawa Pharmaceuticals Co. company and called FK-506, has the potential to greatly reduce organ rejection in transplant patients--and to compete with the only similar drug, cyclosporine. Boger thinks he can increase FK-506's potency and reduce its side effects by using an unproven new technique known as rational drug design. Instead of improving the drug by combining it with other compounds in a process of trial and error, as he might have done at Merck, he will use powerful computers to build a new drug from scratch, atom by atom. He raises money from venture capitalists, hires a team of top researchers, and sets up shop in a ramshackle lab near his alma mater, Harvard University.

But competitors muddy his plans. They beat Vertex to key discoveries, sending its employees on an intellectual and emotional roller-coaster ride. Vertex scientists go through episodes of anger and self-doubt as they feel themselves falling behind. They have screaming matches, fling chairs at walls, and get rip-roaring drunk. Boger, who is both chief scientist and CEO, spends much of his time raising money and setting up joint ventures. Throughout, he is the voice of reason, formulating strategy and soothing sore feelings among his highly competitive, ego-driven staff.

Werth's nearly unlimited access to Vertex enables him to expose the ignoble side of the scientific world. There are arguments about whose names will go on scientific papers, and in what order. Biologists battle with chemists over failed experiments or slow-to-arrive results. Boger decides to launch a project on AIDS, not because he believes Vertex has a competitive advantage but because he knows it will entice investors. And there's a near-mutiny when the company's initial stock offering flounders and the value of employee options plummets.

Most remarkable, in terms of contentious relationships, is Boger's personal and professional rivalry with Harvard Professor Stuart Schreiber, which Werth explores at length. Schreiber, a leading organic chemist and authority on FK-506, is initially on Vertex' scientific advisory board. But it turns out he also has a research deal with a competitor, Roche Holdings Ltd. Although he's guilty of nothing illegal or unethical, Schreiber winds up being kicked out of Vertex and despised by Boger. Vertex' staff remains profoundly fearful that Schreiber could hurt their chances of being the first to develop a drug from FK-506.

Boger doesn't hide his anger or jealousy. At one point, when Nature magazine publishes an article by Vertex scientists on the same day as another journal publishes a similar article by Schreiber, Boger says: "I want to rub his nose in the dirt and step on his head. But I'll settle [for a tie]."

Boger, an arrogant and self-confident scientist, spends a lot of time plotting ways to beat the competition. And while Werth's accounts of his calculating approach are engaging, the author is not entirely objective. Aside from Schreiber, his primary sources are Boger, the Vertex staff, and a handful of others who provide background. He would have done well to seek more sources.

Werth reports that Merck beat Vertex in developing a potential AIDS drug--but doesn't mention that several other companies have developed similar compounds. There's also a dearth of reporting on the fate of FK-506, which is now up for approval by the Food and Drug Administration. At the end of the book, Boger suddenly decides to change course and develop the drug for an entirely new purpose: combating multidrug resistance in cancer patients receiving chemotherapy. Did other companies give up as well? Was Boger admitting defeat? Werth could have finished on a stronger note if he had tried to answer the central question raised by Boger's decision to start Vertex: Has the company, with its use of rational drug design, been any more successful than Merck in developing drugs?

The book's ending comes as no surprise to anyone who has invested in Vertex stock: Even though the company is forging ahead, it has yet to develop a billion-dollar molecule. Still, Werth's narrative is a great read and offers unusual insight into a fledgling industry. Anyone interested in biotech or involved in a startup of any kind should enjoy reading the story of Joshua Boger and his adventures in what Werth calls the "blood sport of big-time science."GEOFFREY SMITH


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