New York Times  [Printer-friendly version]
July 1, 2007

A CHALLENGE TO GENE THEORY, A TOUGHER LOOK AT BIOTECH

[Rachel's introduction: "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."]

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. E-mail:
dcaruso@nytimes.com.