New York Times, July 1, 2007

A Challenge to Gene Theory,
A Tougher Look at Biotech

By Denise Caruso

THE $73.5 billion global biotech business may soon have
to grapple with a discovery that calls into question the scientific
principles on which it was founded.

Last month, a consortium of scientists published findings that
challenge the traditional view of how genes function.
The exhaustive four-year effort was organized by the
United States National Human Genome Research Institute and
carried out by 35 groups from 80 organizations around the world.
To their surprise, researchers found that the human genome might
not be a tidy collection of independent genes after all, with each
sequence of DNA linked to a single function, such as a
predisposition to diabetes or heart disease.

Instead, genes appear to operate in a complex network, and
interact and overlap with one another and with other components
in ways not yet fully understood. According to the institute,
these findings will challenge scientists to rethink some long-held
views about what genes are and what they do.

Biologists have recorded these network effects for many years in
other organisms. But in the world of science, discoveries often do
not become part of mainstream thought until they are linked to
humans.  With that link now in place, the report is likely to have
repercussions far beyond the laboratory. The presumption that
genes operate independently has been institutionalized since
1976, when the first biotech company was founded. In fact, it is
the economic and regulatory foundation on which the entire
biotechnology industry is built.

Innovation begets risk, almost by definition. When something is
truly new, only so much can be predicted about how it will play out.
Proponents of a discovery often see and believe only in the
benefits it will deliver. But when it comes to innovations in food
and medicine, belief can be dangerous. Often, new information is
discovered that invalidates the principles thus the claims of
benefit and, sometimes, safety on which proponents have built
their products.

For example, antibiotics were once considered miracle drugs that,
for the first time in history, greatly reduced the probability that
people would die from common bacterial infections. But doctors
did not yet know that the genetic material responsible for
conferring antibiotic resistance moves easily between different
species of bacteria. Overprescribing antibiotics for virtually every
ailment has given rise to superbugs that are now virtually unkillable.

The principle that gave rise to the biotech industry promised
benefits that were equally compelling. Known as the
Central Dogma of molecular biology, it stated that each gene in
living organisms, from humans to bacteria, carries the information
needed to construct one protein. Proteins are the cogs and the
motors that drive the function of cells and, ultimately, organisms.
In the 1960s, scientists discovered that a gene that produces one
type of protein in one organism would produce a remarkably
similar protein in another. The similarity between the insulin
produced by humans and by pigs is what once made pig insulin
a life-saving treatment for diabetics.

The scientists who invented recombinant DNA in 1973 built their
innovation on this mechanistic, one gene, one protein principle.
Because donor genes could be associated with specific functions,
with discrete properties and clear boundaries, scientists then
believed that a gene from any organism could fit neatly and
predictably into a larger design; one that products and companies
could be built around, and that could be protected by
intellectual-property laws.

This presumption, now disputed, is what one molecular biologist
calls the industrial gene.

"The industrial gene is one that can be defined, owned, tracked,
proven acceptably safe, proven to have uniform effect, sold and
recalled", said Jack Heinemann, a professor of molecular biology
in the School of Biological Sciences at the
University of Canterbury in New Zealand and director of its
Center for Integrated Research in Biosafety.

In the United States, the Patent and Trademark Office allows
genes to be patented on the basis of this uniform effect or
function. In fact, it defines a gene in these terms, as an ordered
sequence of DNA that encodes a specific functional product.

In 2005, a study showed that more than 4,000 human genes had
already been patented in the United States alone. And this is but
a small fraction of the total number of patented plant, animal and
microbial genes. In the context of the consortium's findings, this
definition now raises some fundamental questions about the
defensibility of those patents.

If genes are only one component of how a genome functions,
for example, will infringement claims be subject to dispute when
another crucial component of the network is claimed by someone
else? Might owners of gene patents also find themselves liable for
unintended collateral damage caused by the network effects of the
genes they own?

And, just as important, will these not-yet-understood components
of gene function tarnish the appeal of the market for biotech
investors, who prefer their intellectual property claims to be
unambiguous and indisputable?

While no one has yet challenged the legal basis for gene patents,
the biotech industry itself has long since acknowledged the
science behind the question.

"The genome is enormously complex, and the only thing we can
say about it with certainty is how much more we have left to
learn", wrote Barbara A. Caulfield, executive vice president and
general counsel at the biotech pioneer Affymetrix,
in a 2002 article on Law.com called Why We Hate Gene Patents.

"We're learning that many diseases are caused not by the action
of single genes, but by the interplay among multiple genes",
Ms. Caulfield said. She noted that just before she wrote her
article, scientists announced that they had decoded the genetic
structures of one of the most virulent forms of malaria and that
it may involve interactions among as many as 500 genes.

Even more important than patent laws are safety issues raised by
the consortium's findings. Evidence of a networked genome
shatters the scientific basis for virtually every official risk
assessment of today's commercial biotech products, from
genetically engineered crops to pharmaceuticals.

"The real worry for us has always been that the commercial
agenda for biotech may be premature, based on what we have
long known was an incomplete understanding of genetics", said
Professor Heinemann, who writes and teaches extensively on
biosafety issues.

"Because gene patents and the genetic engineering process itself
are both defined in terms of genes acting independently", he said,
"regulators may be unaware of the potential impacts arising from
these network effects."

Yet to date, every attempt to challenge safety claims for biotech
products has been categorically dismissed, or derided as
unscientific. A  2004 round table on the safety of biotech food,
sponsored by the Pew Initiative on Food and Biotechnology,
provided a typical example:

"Both theory and experience confirm the extraordinary
predictability and safety of gene-splicing technology and its
products", said Dr. Henry I. Miller, a fellow at the Hoover Institution
who represented the pro-biotech position. Dr. Miller was the
founding director of the Office of Biotechnology at the
Food and Drug Administration, and presided over the approval
of the first biotech food in 1992.

Now that the consortium's findings have cast the validity of that
theory into question, it may be time for the biotech industry to
re-examine the more subtle effects of its products, and to share
what it knows about them with regulators and other scientists.
This is not the first time it has been asked to do so. A 2004
editorial in the journal Nature Genetics beseeched academic and
corporate researchers to start releasing their proprietary data to
reviewers, so it might receive the kind of scrutiny required of
credible science. ACCORDING to Professor Heinemann, many
biotech companies already conduct detailed genetic studies of
their products that profile the expression of proteins and other
elements. But they are not required to report most of this data to
regulators, so they do not. Thus vast stores of important
research information sit idle.

"Something that is front and center in the biosafety community in
New Zealand now is whether companies should be required to
submit their gene-profiling data for hazard identification",
Professor Heinemann said. "With no such reporting requirements,
companies and regulators alike will continue to blind themselves
to network effects", he said. The Nature Genetics editorial, titled
Good Citizenship, or Good Business?, presented its argument as
a choice for the industry to make. Given the significance of these
new findings, it is a distinction without a difference.

--------------------------------------------------

Denise Caruso is executive director of the Hybrid Vigor Institute,
which studies collaborative problem-solving.
She is the author of Intervention a book detailing the risks of
biotech technology.
Intervention can be purchased at Amazon.com

E-mail Denise at : dcaruso@nytimes.com
You're listening to
"Across The Universe"
by John Lennon