A Challenge to
Gene Theory, a Tougher Look at Biotech
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
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
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
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
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.
[correction: that title denotes a
different dogma - Crick's slogan that the info flows only
one-way from DNA to RNA to protein. The other 1960s slogan'one
gene/one protein' might be attributed to Ch. Anfinsen, but has not
generally been, nor has it been deemed a dogma; anyhow it is not the
"central dogma" - RM]
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
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
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
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
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
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
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
"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
"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
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
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
With no such reporting requirements, companies and regulators
alike will continue to "blind themselves to network effects," he
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