[procaare] Research Rebel Challenges Scientific Publishing

[AEGiS <procaare@usa.healthnet.org>]

Research rebel gets word out: Biochemist rallies colleagues to publish results on the
Web -- not in high-priced journals

[* Mod note - this is an important article and we applaud the efforts of Pat Brown. With
HIV affecting millions all over the world, access to information is vital and not only are
scientific papers in often inaccessible high-priced journals but also, material cannot be
shared or reproduced due to copyright laws. If we are challenging governments and drug
companies to see the current situation as an emergency and are forcing drug price cuts and
changes to patent and compulsory licensing laws on medications - the control of
life-saving information must be challenged as well.*]

Research rebel gets word out: Biochemist rallies colleagues to publish results on the
Web -- not in high-priced journals
San Francisco Chronicle - Monday, September 2, 2002
Tom Abate, Chronicle Staff Writer
http://ww2.aegis.org/news/sc/2002/SC020901.html
***************

Pat Brown, a biochemist at Stanford University, invented a cheap way to put thousands of
bits of DNA on test slides, helping to pave the way for industrial-scale studies of how
genes control cells. But spying out the secrets of cells is not what he likes to talk
about these days.

Brown has a new scheme in mind: He wants to raise about $20 million in foundation grants
to bring together top scientists to review scientific research, and publish it on the
Web -- for free.

"We'll just give it away" to undercut the pricey subscription journals that dominate
academic publishing, Brown said.

"A high school student in San Jose could read the latest paper in cell biology," he said.
"Scientists in the Third World could see scientific articles they can't afford. These
people are totally disenfranchised from the latest evidence-based science."

At a time when patents and venture capital are turning universities into corporate
spawning grounds, the 47-year-old Brown is a throwback to the days when prestige was the
main payoff for invention and scientists raced to make knowledge public.

"Pat is a populist," said Harold Varmus, the Nobel laureate and former UCSF professor who
has endorsed Brown's dream of creating a so-called Public Library of Science. "He is
interested in getting the science that the government pays for out there to the people."

As populists so often do, Brown has ruffled feathers, even at Stanford, where he is a
Howard Hughes Medical Institute investigator and popular mentor for young
scientists-in-training. Brown once compared journal publishers to plantation owners.

"Pat has said some harsh things about (scientific) publishing and the people who do it,"
said Donald Kennedy, the former Stanford president who now serves as editor in chief of
Science, the nation's top scholarly journal.

'A BIT OF AN IDEOLOGUE"

Kennedy said he has "enormous respect for Pat as a scientist and a thinker. " Then he
added: "He is certainly a populist. He is zealous. I think he is a bit of an ideologue."

Brown admitted he can get carried away. "More than once I've wished I could go back in
time and not press the send button on an e-mail or suck those words back in my mouth," he
said.

But supporters say if Brown upsets the scientific establishment, it's for the right
reasons.

"He is truly an idealist," said UCSF Professor Joe DeRisi, who worked with Brown in the
1990s, when the Stanford professor posted plans for building cheap DNA microarrays -- a
tool for fast, large-scale gene analysis -- on the Web, free to any scientist with an
Internet connection.

Born at the height of the Cold War, Patrick O. Brown was the second of six children to
arrive in a family that roamed the world to accommodate his father's somewhat mysterious
career in government service. "I didn't realize he was in the CIA until I was a teenager,"
Brown said.

Even as a boy, he said, he always knew he'd be a scientist. But unlike some academics, he
never stayed focused on a single narrow interest. He would have been a mathematician, "for
the sheer fun of it," but chose pediatrics, only to be turned down by Stanford Medical
School. Brown eventually enrolled at the University of Chicago, where his mentor, Nicholas
Cozzarelli, now at UC Berkeley, helped him land a promising research post.

In 1985, Brown, then 31, began work as a postdoctoral fellow in the UCSF laboratory of J.
Michael Bishop and Harold Varmus. By then, the UCSF duo had shown how defects in certain
genes could ignite tumors, a feat for which they shared the 1989 Nobel Prize in Medicine
.It was a coup for Brown to grab bench space as a postdoc in one of the country's hottest
labs, and he made the most of it.

In 1987, Brown showed how HIV, the AIDS virus, splices itself into the genome of the cells
it infects. The work pointed drug developers toward a new way to fight the disease.

IMPRESSED A NOBEL LAUREATE

Although progress toward a drug has been disappointingly slow, publication of the HIV
discovery impressed the right people, including Stanford Nobel laureate Paul Berg.  "That
was the paper that attracted me and why we recruited him," Berg said.

When Brown joined the Stanford faculty in 1988, it was expected he would continue research
on viral diseases, but he soon shifted his focus to what ultimately became the DNA
microarray. Brown wanted to create a tool to help figure out which genes are active in any
given cell at any given time. As he explained it, every cell with a nucleus carries a
complete copy of the 35,000 or so human genes. But most of these genes are inactive. Cells
activate only the genes they need. That's one reason skin cells, for instance, differ from
muscle cells.

Working with collaborators at Stanford's school of engineering, Brown spent the early
1990s developing robotic systems to deposit microscopic fragments of known genes onto
glass slides called DNA microarrays. To find out which genes are active in a tissue
sample, a researcher could drop the sample onto the microarray. The gene fragments on the
array act like smart Velcro, grabbing only the matching genes out of the sample. Brown
also created ways to detect these microscopic matchups, giving researchers a new way
to take snapshots of gene activity in cells.

The paper Brown published in 1995 described a technology that wasn't entirely novel. In
1991, Stephen Fodor and colleagues at the Affymax Research Institute in Palo Alto
published a strategy for creating microarrays that would employ a process akin to that
used to make silicon chips. Fodor's method formed the technical heart of Affymetrix, the
Santa Clara biotech firm he founded to sell his brand of arrays.

'HOME BREWS' ON THE WEB

 From the start, however, Brown wanted to create a process any competent lab could use to
make its own arrays for an initial investment of about $25,000. He posted instructions for
making these so-called "home brews" on the Web. Together, Brown's cheap home brews and
Fodor's pricier but more powerful chips have revolutionized the genetic analysis of tissue
samples.

Now, Brown's wandering eye has turned to a new challenge: reforming the way scientific
papers are published.

There are more than 8,000 scientific and technical journals in the world today. Some are
produced by nonprofit societies such as the American Association for the Advancement of
Science, the publisher of Science. Many of the rest are created by for-profit firms, such
as the Anglo-Dutch publisher Reed Elsevier.

Both for-profit and nonprofit journals use top scientists to review new experiments for
accuracy and credibility, a process called peer review. Because journals usually have few
readers, annual subscriptions are costly. A popular journal like Science costs $150. A
niche chemistry journal like Reed Elsevier's
Tetrahedron Letters can run $8,000.

But cost wasn't all that bothered Brown. He thought that science publishing was a paper
dinosaur in a digital world. He saw how physicist Paul Ginsparg, now with Cornell
University, had created an online repository for new papers in that field during the
1990s.

"Pat submerged himself in this guy's writings and got excited about doing something like
that on a wider scale," said Varmus, who signed the letter Brown wrote to Science in March
2001, calling for creation of a Public Library of Science.

His idea, developed with help from geneticist Michael Eisen at the Lawrence Berkeley
National Laboratory, was that six months after they published any new paper, scientific
journals should pour all their content into a free, public database.

More than 30,000 scientists ultimately endorsed the letter Brown and Eisen posted on the
Web. One line in that letter particularly irked publishers: Signers pledged to "publish
in, edit or review for, and subscribe to" only journals that followed the six-month rule.

"I don't think the threat of a boycott is the way to start a conversation," said Kennedy,
the Science editor.
The implied threat proved empty.

Academics need journals more than journals need academics, said David Stern, a Yale
University science librarian who has followed the fray. "It's publish or perish," Stern
said. "As long as we have promotion and tenure tied to publishing, change won't work."

A TOUGH ROAD AHEAD

Rebuffed in his initial bid to reform the system, Brown now hopes to raise enough
foundation money to launch a new set of online journals that will be free to readers. If
he succeeds, and there's no certainty yet he'll even get to try, scientific publishing
might have to radically revamp price and exclusivity policies.

His would-be targets think Brown has bitten off more than he can chew.

"If he thinks he has a better way, good luck and welcome to publishing," said Karen Hunt,
a senior vice president at Elsevier.

Brown is sticking to his guns, hoping soon he'll be able to put some foundation money
where his mouth is.

"I am an ideologue, if you want to call it that," he said. "This stuff should be in the
public domain. It should not be in private hands."


E-mail Tom Abate at tabate@sfchronicle.com.

Copyright (c) 2002 - San Francisco Chronicle Press. All rights reserved.

Source:  [AEGiS]

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