The Accidental Author or
the Price of Popularity

By Mika Ono

Why did Tamas Bartfai and Graham Lees write Drug Discovery: From Bedside to Wall Street, a book that addresses topics such as what makes a successful drug, why so few diseases are treatable, and how patients, investors, regulators, and scientists fit into the process?

It all started a few years ago because Bartfai had a problem. He was getting tired of repeating himself.

When Bartfai joined The Scripps Research Institute from the pharmaceutical industry in 1999, he found that his newfound academic colleagues were eager to learn about drug development. And—as former head of central nervous system research at Hoffman-La Roche and one of the developers of Zimelidine, the first selective serotonin reuptake inhibitor (SSRI) and other central nervous system drugs for Astra (now AstraZeneca) and later for Roche —Bartfai had an overview of the complex drug discovery process. At the time, this made Bartfai a rarity, although he points out that since then a number of investigators have come to Scripps Research from the pharmaceutical industry.

 "I didn't realize how unique my perspective was," says Bartfai, who directs Scripps Research's Harold L. Dorris Neurological Research Institute and chairs the Molecular and Integrative Neurosciences Department (MIND). "But then again no schools teach you how to make a drug. Schools teach you how to be a biologist, a chemist, an M.D… To understand drug development, you have to work in 'Big Pharma.'"

So Bartfai found himself on the phone, in the halls, after meetings, explaining the pharmaceutical industry from the ground up to scientists who were extremely accomplished in their fields. At first, he was happy to oblige. Then, although still committed to academic exchange and collegiality, he became tired of hearing himself talk.

Setting the Stage

At that point, Julius Rebek, director of Scripps Research's Skaggs Institute for Chemical Biology, had an idea. If Bartfai was so tired of repeating himself, why didn't he give a series of lectures? That way, he could share his knowledge with more than one person at a time.

Hoping to put to rest the questions once and for all, Bartfai agreed to give three lectures on drug discovery. In the presentations, Bartfai aimed to lay out the building blocks of the pharmaceutical industry, emphasizing that these companies are for-profit organizations whose interest in a topic can change dramatically for nonscientific reasons.

"Science is a very small part of it—a very small part," he says. "Science doesn't decide which drugs to create, the market does. Science doesn't decide when to stop, the market does. Science decides which target to pick—and that's about all. And of the total cost, science is a tiny piece, 15 or 20 percent. "

Bartfai prepared a low-key talk for the 30 people from campus he expected at the first lecture.

Four hundred arrived. Some had flown down from San Francisco to hear him speak. Others came from neighboring institutions such as the University of California, San Diego, and the Salk Institute. The audience ranged from department chairs and Nobel laureates to graduate students and postdoctoral fellows to a substantial number of venture capitalists.

Bartfai had to adjust his approach to the lectures. But worst of all, from Bartfai's point of view, was that after the series was over it was deemed such a success that he was asked to repeat it. He refused.

"No jokes can be told twice," he says.

But Rebek had another suggestion. What did Bartfai think about writing a book?

A Book is Born

Thus, Drug Discovery: From Bedside to Wall Street was conceived. But its birth was not without complications.

Bartfai teamed up with co-author Graham V. Lees, a writer and editor whom Bartfai had known for many years and who is now founding editor and publishing director of TheScientificWorld, Ltd., an online scientific and medical publisher. They began 10 months of intensive work on the book project, choosing topics to cover that would interest a wide cross-section of people—from scientists to investors, from patients to policy makers.

As such, Drug Discovery is not a tome to be read straight through from cover to cover, but rather a compilation of chapters to be approached selectively. Some chapters, such as "Raising and Rising Expectations," will appeal to anyone interested in the pharmaceutical industry and its impact on people's lives. Other chapters, such as "Linking Putative Targets to Disease States" are technical enough for scientists to explore the nuts and bolts of drug development.

Among the book's intended audience are graduate students, especially those considering a career in the pharmaceutical industry.

"I want graduate students to understand better the big machine they are joining," Bartfai says. "If the book helps two young chemists make it in industry who wouldn't have otherwise, it will have been worth it. For more experienced scientists who have consulted for industry, I hope they get a sense of déjà vu—an understanding of why some events may have happened the way they did."

While most publishers Bartfai and Lees approached wanted to produce the book in hardcover (and to price it accordingly), Bartfai insisted the book appear in paperback. In the end, Bartfai had his way. Plans were made for a paperback sold at $29.95, within reach of the average graduate student.

Market Forces, Take Two

But Bartfai's struggles with the publishing industry weren't over.

As Bartfai and Lees were putting the finishing touches on the manuscript in the fall of 2004, the Vioxx story hit the headlines. A study had shown that Vioxx, which had been approved by the U.S. Food and Drug Administration to treat pain and inflammation in arthritic and other conditions, increased the risk of heart attack and stroke. In a cloud of negative publicity, Merck & Co. withdrew the drug from the market.

Some members of the publishing industry recognized Bartfai and Lees' book as an opportunity to cash in on the controversy. Barfai explains his response in a letter to colleagues.

"I have been asked by some publishing houses that were interested in publishing the book to add eye-catching, public pleasing VIOXX-case inspired condemnations of pharmaceutical companies to the title and to the text, to ride a wave of such popular and well selling books of the year 2004," he writes. "I have resisted this request because my experience is that 99% of all colleagues I have worked with in the industry are honest, hard working, very competent scientists who want to make a novel medicine to treat patients and I have no reason, based on my 30 years of encounters with these pharma researchers, to doubt them or assume that they changed in the past years and on purpose endanger patients. Luckily, Elsevier/Academic Press agreed."

In the end, the book makes only passing reference to the Vioxx case. While Bartfai and Lees explore at length the issue of how to improve the system of drug development, the tone remains balanced and constructive.

Even without Vioxx-related hype—or perhaps because of its absence—the book seems to have found its audience. Floyd Bloom, professor emeritus at Scripps Research and CEO of Neurome, Inc., for example, finds that the book offers important insights. "Anyone who thinks solutions to drug development are just around the corner would be well-advised to get this insider's views as to where the real problems lie," he comments.

These days, when Bartfai becomes tired of hearing himself talk about the process of drug discovery, he can direct his colleagues to his chapters.

But he's still being asked to repeat himself. Now publishers are after Bartfai to write another book.

For more information on Drug Discovery: From Bedside to Wall Street, see Elsevier's web site. All Bartfai's proceeds are donated to support stipends at Scripps Research.

Send comments to: mikaono[at]scripps.edu

Scripps Research Professor Tamas Barfai offers an unusual overview of the drug discovery process.

A portion of the proceeds from Drug Discovery: From Bedside to Wall Street will fund stipends at Scripps Research. For more information on the book, see Elsevier's web site.