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 the way 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, like 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 that it will deliver.
But when it comes to innovations in food and medicine, belief can be a
dangerous thing. 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.

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
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," 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 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
Miller, a fellow at the Hoover Institution who represented the pro-biotech
position.

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 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. That means that 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," 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.


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