Future pharmers Biotech firms using plants in attempt to produce proteins faster, cheaper

At a greenhouse in Vacaville, scientists are betting
on an unlikely plant in their effort to treat a certain
type of cancer: tobacco.

Scientists at Large Scale Biology Corp. are using
genetic engineering techniques to turn rows of
tobacco seedlings into organic factories, producing a
medicinal protein that may treat non-Hodgkin’s
lymphoma.

Tom Abate, Chronicle Staff Writer

The experiments going on here are just one example
of a new field called biopharming — the attempt to
produce biotech medicines in plants.

For the last two decades, biotech proteins have been
made by splicing human genes into bacteria,
mammalian cells or fungi. Large quantities of these
fast- growing cells are brewed in fermentation vats.

Biopharming advocates think living plants — corn,
soybeans and tobacco are the current favorites — can
produce protein medicines faster and cheaper than
the stainless steel fermentation factories that can
cost tens, if not hundreds,

of millions of dollars to build.

"Plants are a way to lower the capital barriers and
costs," said Mich Hein, president of Epicyte
Pharmaceutical, a San Diego firm experimenting with
several medicinal proteins in corn.

Experimenting is the operative word.

The U.S. Food & Drug Administration has not yet
approved a plant-produced medicine for human use.
Biopharming pioneers such as Ventria Bioscience of
Sacramento, ProdiGene in Texas and Meristem
Therapeutics in France are at various early stages in
the FDA’s process of reviewing the safety and
efficacy of new medicines.

But biotech critics say the FDA and the U.S.
Department of Agriculture, which share supervision of
biopharming, need better rules to make sure plant-
produced biotech proteins don’t jump into the food
supply.

"With food crops grown in open air fields, we think
the risk is too great," said Bill Freese, who recently
authored a 97-page report on the topic for the
environmental group Friends of the Earth. "We think
very carefully controlled biopharming could proceed
with non-food crops in greenhouses."

Proponents and opponents of biopharming agree on
at least one point — the practice is still young. After
reviewing government records going back to 1991,

Freese counted about 400 biopharm products being
grown in test plots that total about 1,600 acres.

These experiments take a wide variety of
approaches. In Vacaville at Large Scale Biology, for
instance, a genetically engineered virus is the
delivery vehicle used to help introduce human genes
into the tobacco seedlings.

The virus infects the plant’s cells with human genes.
Once there, the infected cells produce the protein
drug as a byproduct of the plant’s growth. Other
biopharming pioneers use different tactics to turn
their plants into production vectors.

The regulatory framework governing the practice is
also still young and fluid. The USDA issues the
permits that companies need in order to field test a
plant-produced biopharmaceutical. It also mandates
the practices designed to prevent cross-pollination or
other forms of contamination of food crops.

These measures include requiring separations of half
a mile or more between certain biopharm crops and
their food counterparts, and training and monitoring of
the agricultural workers.

The FDA steps in when a company proposes to give
a biopharmed protein to a human patient. For
instance, Large Scale Biology recently completed an
FDA Phase I safety study in which 16 patients took
the medicinal protein grown in tobacco plants.

Biopharming proponents fear the controversy over
genetically engineered foods will spill over into their
area and stifle the industry. They stress that
plant-produced medicines can have safety benefits.

Take ProdiGene, the Texas firm that is close to
seeking approval to sell an enzyme called trypsin
that it grows in corn.

Trypsin is not a drug, but a chemical used to help
make insulin or work with cell cultures. It is currently
derived from the pancreatic tissue of cows and pigs,
sources that have become suspect.

"There is real pressure to get away from anything
that uses animal products,

for fear of mad cow disease," said ProdiGene Vice
President Joseph Jilka.

ProdiGene officials said a 400-acre cornfield could
grow enough trypsin to supply about 5 percent of the
total market. On the flip side, biopharming opponents
say these large fields will pose a bigger risk that
genetically engineered genes will jump into the food
supply.

Critics point to the StarLink episode to bolster their
view in the jumping genes debate. In 1998, biotech
opponents found traces of StarLink, a genetically
engineered corn approved for animal feed but not for
human consumption, in taco shells and other
consumer products.

Skeptics say StarLink proves that industry can’t be
trusted to keep biopharmed crops separate from the
food supply. But Lisa Dry, spokeswoman for the
Biotechnology Industry Organization in Washington,
D.C., said ordinary farming is completely different
from biopharming, which involves better trained staff
and stricter regulatory oversight.

"This is night and day," Dry said. "These crops are
not really crops, they are laboratory facilities."

The USDA and FDA are supposed to be coming out
with new joint guidelines for biopharm products, but
the rules have been repeatedly delayed. The Bush
administration recently added a pre-review process to
the oversight of genetically engineered food crops,
but Dry said biopharmed products don’t fall under
those rules.

Any move to stop biopharmers from using food crops,
or to force them into greenhouses, would crimp the
industry. Corn, now the most popular biopharm crop,
would be particularly difficult to enclose. Industry is
hoping to dodge opponents’ demands for greenhouse
enclosures.

Meristem, a French firm developing medicinal
proteins in corn and tobacco, says it has had very
little trouble from protesters in a country where
GMOs — the shorthand for genetically modified foods
— are anathema.

"The public reacts quite negatively to GMOs in
agriculture," said Sancha Salgueiro, a Meristem
scientist. "But to our great fortune they react quite
well to GMOs for drugs."

There have already been protests in the United
States. Last summer, Greenpeace picketed a rice
field in Sutter County where Sacramento-based
Ventria was biopharming rice. Ventria Chief
Executive Scott Deeter said it is extremely unlikely
that there would be cross-pollination between
biopharmed and food rice because rice is
self-pollinating, unlike corn.

Ventria is biopharming rice that contains lysozyme,
the infection-fighting protein found in tears and saliva.
It hopes to sell its rice-based lysozyme to animal
feed makers as a substitute for the antibiotics they
now add to feeds —

a practice blamed for helping breed drug-resistant
bacteria.

Biopharming technologies in the wings would further
minimize any environmental fallout. AltaGen
Bioscience of Morgan Hill is in the early stages of
producing protein medicines in hydroponically grown
potato plants.

"We would be able to do this in greenhouses," said
AltaGen Chief Executive Rick Srigley. "We will be
insulated from the natural environment."

— Further study: The Pew Charitable Trust recently
held a conference to discuss the promise and perils
of biopharming, and much of the material is online at
pewagbiotech.org/events/0717/. The Friends of the
Earth report is available at http://www.gefoodalert.org.

http://www.sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/2002/08/12/BU121171.DTL&type=business