GENET archive


2-Plants: Update on GE pharma plants

                                 PART I
------------------------------- GENET-news -------------------------------

TITLE:  New drug technique wins OK
SOURCE: Des Moines Register, USA, by Philip Brasher
DATE:   1 Feb 2006

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New drug technique wins OK

Washington, D.C. -- Dow AgroSciences has won the first federal approval
of a plant-made vaccine, the product of a laboratory process that avoids
the controversial use of pharmaceutical field crops.

The chicken vaccine will not be commercialized, but officials with Dow
AgroSciences said Tuesday that winning approval from the U.S.
Agriculture Depart- ment's Center for Veterinary Biologics in Ames, Ia.,
showed the promise for making pharmaceuticals from plant cells, rather
than animal products or whole plants.

"We felt it was extremely important to understand whether or not this
technology platform could meet" the USDA's regulatory requirements, said
Butch Mercer, the company's global business leader for animal health.

Dow's advance comes amid lingering concerns about using genetically
engineered field crops, such as corn, to produce pharmaceuticals.

Iowa Gov. Tom Vilsack has been pushing the pharmaceutical corn
production, but research in that area has slowed because of strong
opposition from the food industry and a series of highly publicized
mistakes by biotech companies. Food companies fear that pharmaceutical
crops could contaminate ingredient supplies.

Dow AgroSciences, an Indianapolis-based unit of Dow Chemical Co.,
developed its vaccine by fermenting bioengineered tobacco cells in steel

The plant cells produce the antigens used to make the vaccine against
Newcastle disease, a contagious and fatal viral disease affecting all
species of birds.

Vaccines are typically made from chicken eggs or in mammalian cells,
which can carry diseases. The Dow process also uses fragments of the
virus, rather than the entire pathogen, in making the vaccine.

"It's inherently safer because you're not treating an animal with a
virus," said John Cuffe, the company's research and development leader
for animal health.

The plant-made vaccine also does not need cold storage.

Dow has several commercial products in development, all intended for
animals. The first product is not expected to reach the market before
2009 or 2010. There are already several Newcastle vaccines on the market.

"Clearly, the advantage of all this is that it gets around the
containment issue" involved in growing pharmaceutical plants outdoors,
said Stephen Howell, director of Iowa State University's Plant Sciences

The laboratory process would be useful for making products that aren't
needed in large quantities, Howell said.

Making a vaccine from the fermented tobacco cells requires only a
fraction of the material needed for some drugs, such as digestive aids
that would be made from corn.

Stephanie Childs, a spokeswoman for the Grocery Manufacturers of
America, said the food industry welcomed finding methods of drug
manufacturing that "maintain the purity of the food supply."

                                 PART II
------------------------------- GENET-news -------------------------------

TITLE:  Transgenic tobacco with built-in tick-protection
SOURCE: BerlinOnline, Germany, translated by Mark Hucko, Checkbiotech
DATE:   30 Jan 2006

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Transgenic tobacco with built-in tick-protection

Tobacco plants can now produce vaccine against Lyme disease - a tick-
borne disease from the bacterium Borreliosis. Dr. Heribert Warzecha,
from the University of Wuerzburg, Germany, describes how his group was
able to accomplish this feat in the scientific journal Nature
Biotechnology.  Scientists have already several times tried to generate
plant-made vaccines with the aid of genetic engineering. Generally it
works since many vaccines are protein-based, whose building code can be
inserted into the plant hereditary material as DNA. However, until now,
enhanced plants have produced only minute amounts of the desired
substances. In an innovative approach, Dr. Warzecha and his team built
in the additional hereditary information in the tobacco plant's
chloroplasts - not in the cellular nucleus. Chloroplasts are small
cellular organelles with their own hereditary material, which help the
plants to produce energy from sunlight. The advantage: in one cell there
are around one hundred chloroplasts in comparison to only one nucleus.
Thus, plants with transgenic chloroplasts are more effective vaccine
producers, in that the yield of a target protein is much higher than
those that target the nucleus. Dr. Wuerzburg's plants produce an OspA
protein, which is also found on the surface of the bacterium
Borreliosis. However, OspA alone is not suitable as a vaccine. To be
effective it must be combined with fatty acids - and to Dr. Wuerzburg's
fortunes his genetically modified plants were able to accomplish this
combination. Experiments with mice showed that the tobacco vaccine has
comparable effectiveness with vaccines produced in conventional
bacterial cultures. However, it appears that people cannot take
advantage of this protection yet, since Borreliosis vaccines have not
been granted public use by regulatory officials.

(Nature Biotechnology, Bd. 24, S. 76)

                                 PART III
------------------------------- GENET-news -------------------------------

TITLE:  Fighting cancer with the help from plants
SOURCE: by Ana Hrus, Checkbiotech, Switzerland
DATE:   26 Jan 2006

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Fighting cancer with the help from plants

"How to create a better vaccine" - that is the question that occupies
many researchers in the world. Although there is a multitude of vaccines
produced in the 21st Century, it is impossible to use them on a world-
wide scale due to their high cost and methods of application.

A research team from the Biotechnology Foundation Laboratories at the
Thomas Jefferson University in Philadelphia, has been working on
developing an entirely new class of vaccines.

Under the direction of Hilary Koprowski, M.D., they have focused their
efforts on edible plants as a vehicle to produce antigens, which induce
immune responses that can protect against a variety of pathogens. Such
vaccines are less expensive to produce compared to the current vaccines,
they are safe, effective and suitable for widespread distribution even
through the developing countries.

In the publication in PNAS by Kisung et al., "Inhibition of tumor growth
by plant-derived mAb," Dr. Koprowski's research group reported the
production of functional anti-tumor antibodies in tobacco. They
demonstrate successful production of plant-derived antibody CO17-1A,
which recognizes a specific type of cancer called Adenocarcinoma.

Tumor cells display a variety of specific molecules on their surfaces
that distinguish them from normal cells. These molecules are called
tumor antigens. Adenocarcinoma, a form of cancer, contains a large
amount of the antigen called GA733 on its cell surface, which the
antibody CO17-1A recognizes.

The displayed antigens can then be recognized by antibodies that are
specific to the given antigen. That way the organism recognizes foreign
molecules and initiates an immune response. Due to the antibody-antigen
recognition property, antibodies are often used in research for the
detection of antigens. Even more importantly, they can also be used for
the therapeutic purposes.

Dr. Koprowski's research team first step was to generate transgenic
tobacco plants (Nicotiana tabacum) that were able to produce the desired
antibodies. Once the tobacco plants reached a certain growth stage, the
researchers harvested the leaves. The antibodies were prepared from 1 kg
of fresh tobacco leaves.

Once the antibodies were extracted from the tobacco leaves, it was
important to show that they still retained the ability to bind the
antigen GA733-2. Dr. Koprowski's team tested this by using a method
commonly used for protein analysis called, Western Blot.

The Western Blot showed that the plant-derived antibodies had similar
specific binding activity on colorectal cancer cells compared to
conventional monoclonal antibodies produced in mice. Dr. Koprowski's
group reported similar efficiency in inhibiting colorectal tumor growth
in mice in vivo.

Monoclonal antibodies, which have high specificity to a particular
antigen, are commonly produced by immunizing mice and fusion of their
spleen cells to immortalized cells. The procedure is more time consuming
and expensive compared to plant-made monoclonal antibodies. Dr.
Koprowski told Checkbiotech, "The technology will allow the development
of new, desperately needed vaccines and will prevent many of the
diseases currently ravaging the developing world."

Although antibodies produced in plants have different sugar
modifications, Dr. Koprowski's team reports that their antibody still
retained the same activity that a mouse derived antibody had. That
finding is truly significant and opens the door to new possibilities of
functional antibody production.

The scientists of the Biotechnology Foundation Laboratories have so far
developed plant-based vaccines against rabies, respiratory syntial
virus, HIV, anthrax, and colorectal cancer. At present, they are
focusing on developing vaccines against, anthrax, smallpox, SARS, the
common flu, and pediatric vaccines that use plants as a delivery vehicle.

Dr. Koprowski believes that the technology they are developing can and
will change the face of human health worldwide. Inexpensive vaccines
administered by oral consumption, and not requiring the services of
health professionals, will make universal vaccination possible.

Ana Hrus is a Science Journalist for Checkbiotech and is currently
finishing her PhD degree in Cell Biology at the University of Basel,
Switzerland. Contact her at

Original article:
Kisung et al. Inhibition of tumor growth by plant-derived mAb. PNAS, 102
(2005), p. 7026-7030

Corresponding author:

Dr Hilary Koprowski, MD
Thomas Jefferson University
Biotechnology Foundation Laboratories
Room M-81 Alumni Hall
1020 Locust Street
Philadelphia, PA 19107
Telephone: 1-215-503 1420
Fax: 1-215-923 6786

                                 PART IV
------------------------------- GENET-news -------------------------------

TITLE:  AIDS drug may soon be derived from sunflowers
SOURCE: Seed Magazine, USA, by Leslie Taylor
DATE:   25 Jan 2006

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Flower Power
AIDS drug may soon be derived from sunflowers

Ralph Waldo Emerson described flowers as a "proud assertion that a ray
of beauty outvalues all the utilities of the world." Perhaps this is so,
but recent research shows that sunflowers may have value outside of
beauty. The flower that starred in Van Gogh's paintings can do more than
looking good and providing us with yummy seeds--it may be a source of an
affordable drug to fight AIDS. In his doctoral thesis at the Bonn Centre
of Molecular Biotechnology (CEMBIO) Claudio Cerboncini studied the
sunflower's response to "white stem rot"--an infection caused by the
fungus Sclerotina sclerotiorum. During his work, he isolated compounds
the flowers produce to fight off the invasive mould. One of them,
dicaffeoyl quinic acid (DCQA), is a substance that AIDS researchers have
identified as showing great promise as a new treatment for the disease.
"Dicaffeoyl quinic acid can prevent the HIV virus from reproducing, at
least in cell cultures," Cerboncini said in a press statement released
by the University of Bonn. AIDS drugs typically work by achieving a
stable immune defense condition--slowing the rate at which the virs
replicates until it is equal to, or slower than, the rate at which
infected cells die. Three enzymes--reverse transcriptase, protease and
integrase--are required for virus replication. Unlike most existing AIDS
drugs, which inhibit reverse-transcriptase or protease, DCQA inhibits
integrase. Because integrase is not normally active in human cells,
drugs targeting integrase may have fewer side effects--anorexia, fatigue,
fevers and nausea to name a few--than the current crop of drugs.The catch
is that it's very expensive to manufacture DCQA. The few known natural
sources of the substance, such as artichoke and wild chicory, yield only
miniscule amounts of the compound. As a result, the current market price
for DCQA is about $1,200 (or ?1,000) per mg. Ralf Theisen, a plant
biotechnology researcher at CEMBIO, has patented a method to produce
DCQA more efficiently, using sunflowers and bacteria. By comparing genes
from infected and non-infected plants, Theisen plans to identify the
sunflower gene responsible for production of DCQA. "We can use isolated
enzymes--use the DNA or RNA to transform bacteria so that they can
produce it," Theisen said. "That is most likely a cheaper way than the
chemical synthesis." With this method, DCQA could be produced on an
industrial basis. Theisen and his colleagues at the Julich Research
Center are looking for partners in industry to help them produce the
compound on a large scale. An affordable source of DCQA would make
further clinical tests of the integrase inhibitor feasible. If DCQA
turns out to be as effective a treatment as is hoped, sunflowers could
add more than color to the lives of over 40-million people living with
HIV/AIDS worldwide.

                                 PART V
------------------------------- GENET-news -------------------------------

TITLE:  Biopharming group plans policy recommendations
SOURCE: The Oregonian, USA, by Alex Pulaski
DATE:   24 Jan 2006

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Biopharming group plans policy recommendations
Should medicines be grown on Oregon farms by genetically altering plants?

The Biopharming Ad Hoc Committee, meeting Monday for the third time
since being formed last year, expects to recommend biopharming policies
to Gov. Ted Kulongoski by September. Equally representing agricultural
and public-health interests, the 10-member committee grew from a failed
bill in 2005 that would have put a four-year state moratorium on
biopharming. Oregon currently does not have any acreage planted with
crops whose genes have been altered by pharmaceuticals, usually
proteins. Neil Hoffman, who oversees the regulation of genetically
modified crops under the U.S. Department of Agriculture, said
biopharmaceutical plantings nationally are expected to rise this year
from the 82 acres planted a year ago. Federal records show that three
release permits are pending for biopharmaceuticals to be planted in
Washington state. Hoffman, speaking to the committee by telephone
Monday, described federal oversight, including requirements that
shipments be tracked, that equipment not be used with other crops and
that fields be isolated and subject to inspection. Inspection and other
issues drew fire in a recent audit report by the federal Agriculture
Department's Office of Inspector General. Contrary to the department's
public announcements, the report found, it was not inspecting planted
fields five times a year. "It's true that in the first year the target
was very poorly met," Hoffman acknowledged, but he said the frequency of
inspections had increased since 2003.

                                 PART VI
------------------------------- GENET-news -------------------------------

TITLE:  Commingling issue with pharma-crops
SOURCE: Delta Farm Press, USA, by David Bennet
DATE:   19 Jan 2006

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Commingling issue with pharma-crops

A year after issues surrounding genetically engineered rice first hit
the Missouri Bootheel, a new report finds the benefits of pharma-crops
to producers aren't as grand as first hoped. The report, authored by
Robert Wisner, an economics professor at Iowa State University, says any
claims regarding high farmer compensation and booming pharma-crop
acreage are likely overblown.

But readers beware: while Wisner doesn't claim adherence to their
beliefs, the study was commissioned by the Union of Concerned Scientists
(UCS), an organization deeply suspicious and critical of the pharma-crop

"Agriculture has been in a transitional period from being primarily food-
and-fiber production to being a source for both energy and food," said
Wisner. "That transition has gone relatively smoothly.

"But we've now run into a third stage, a further transition from food,
fiber and energy to pharmaceutical drugs. We're in the extremely early
stages but this latest transition has turned out to be very complicated.
It's not clear where the pharma-crop industry will end up."

Many of the issues involved in pharma-crops center on whether they can
be separated from food and feed supplies so there's no risk of
commingling. Early in 2005, the importance of this was driven home as
fears about commingling, and resulting market problems, at least
temporarily derailed plans to grow pharma-rice in the Missouri Bootheel.

"The fear of mixing pharma-crops with food adds many unknowns. One is:
does the present system and regulations provide for that separation?
Many have stressed the extreme importance of avoiding any commingling."

The Union of Concerned Scientists has concluded that significant changes
are needed in order to insure complete separation, said Wisner.

"Looking at the economic impacts, one of the first questions is, 'What
will be the cost of maintaining the kind of total isolation from food
and feed supplies?' At this point, we don't know. But it will affect net
returns to farmers and net benefits to users of pharma-crops. What will
it take to provide such a system? Is the best route sterile male plants?
Sterile seed? Growing the crop in closed facilities? All those are being

Looking at potential returns to growers, the stage the industry is
currently in suggests there will be only modest niche-market
opportunities. This is largely due to the small acreage needed by the
pharma-crop industry.

"One study indicates approximately 10,000 acres of transgenic tobacco
will be needed to supply the world's needs. That's very small acreage
compared to the 230 million acres U.S. farmers devote to grains and
other major crops."

The pharma-rice and barley acreage planned for Missouri is another
example. "That venture is supposed to be for slightly less than 10,000
acres. That's less than 1 percent of the total crop acres in the
northwest part of Missouri, where the rice would be grown. While there
could be more significant acreage later on as the industry develops,
there are no huge short-term benefits for producers."

Wisner also says there's no evidence of benefits to consumers from lower
drug costs due to pharma-crops. "How could we know? There are no actual
pharma-crop drug products yet available to consumers. That's after about
15 years of trials and test plots.

"Pharma-crop industry people indicate the major source of benefits will
likely be reduced production costs. While producing the feed stock
material from crops would involve adding acres, it may take years to
expand conventional pharmaceutical production facilities.

"Again, we don't know the cost for providing the kind of segregation the
food industry is asking for. We also don't have actual examples of
pharma-crop products to say, 'Here, indeed, are the cost savings.'"

According to several sources, said Wisner, the products to be derived
from pharma-rice will actually cost about the same as producing similar
products under conventional production. But it's early in the game, he
admitted, and that could change. "Because of the proprietary nature of
some of the products, there are likely some unknown products that are
yet to surface."

Wisner said given the limited bargaining power of farmers and small
acreage that's anticipated, the primary impact of pharma-crops would
likely be on two business sectors: research work (either private,
university or a combination of the two) and processing.

The pharma-crop industry will undoubtedly point to the fact Wisner's
paper -- the first by a land grant university economist -- was
commissioned by the UCS. While making it clear he isn't part of the UCS,
Wisner isn't cowed.

"First of all, their call for immediate halt of open-air production of
these crops isn't from my report. That's just the organization speaking
and a substantial part of that is based on a study published about a year ago.

"The UCS has been monitoring key pharma-crop issues and hoping to
generate dialogue. From my perspective, the purpose in providing this
report was to look at some of the underlying issues and address what we
know and don't know. And I wanted to point to some of the issues that
need to be examined in pharma-crops.

"If you look at the report carefully, you'll find I attempted to provide
a balance with issues raised especially by the food industry as well as
what's being presented in terms of pharma-crop advantages."

How far out is Wisner projecting?

"This is something that needs constant monitoring. There may well be
changes (requiring number adjustments) in five to 10 years. The success
of pharma-crops hinges heavily on keeping them separate from food and
feed supplies. If that challenge is successfully dealt with, many of the
other challenges in this industry are greatly diminished."

Editor's note: to see Wisner's full report visit

                                 PART VII
------------------------------- GENET-news -------------------------------

TITLE:  Plant-derived plague vaccine protects guinea pigs
SOURCE: Reuters
DATE:   10 Jan 2006

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Plant-derived plague vaccine protects guinea pigs

NEW YORK (Reuters Health) - A vaccine against Yersinia pestis, which
scientists grew in tobacco plants, effectively protected guinea pigs
against a lethal aerosol exposure to this bacterium that causes the
plague, also known as the "bubonic plague," or the "black death," which
killed millions of people in Europe during the Middle Ages. This report
demonstrates the ability of a "rapid and highly scalable" plant
expression system to produce a vaccine that generates an immune response
against Y. pestis and perhaps other potential agents of biological
warfare, the scientists note in the current issue of the Proceedings of
the National Academy of Sciences, Early Edition. The plague is usually
spread by bites of a rodent flea that carries Y. pestis or by handling
an infected animal. Antibiotics are effective against the plague, but if
not treated promptly, the infection is still often lethal. Small
outbreaks of Y. pestis infection still occur in Africa, Asia, and the
Americas and there is a "great need" for improved plague vaccines that
can be manufactured quickly and inexpensively, Dr. Luca Santi from
Arizona State University in Tempe and colleagues point out in the paper.
Santi's group developed a genetically engineered Y. pestis vaccine based
on two key Y. pestis antigens -- F1 and V - proteins that trigger the
body to produce an immune response. These two proteins were successfully
and rapidly grown separately or as a combined fusion protein in the
leaves of tobacco plants. "All of the plant-derived purified antigens,
administered subcutaneously to guinea pigs, generated systemic immune
responses and provided protection against an aerosol challenge with
virulent Y. pestis," Santi and colleagues report. A majority of
vaccinated guinea pigs survived exposure to the plague bacterium and
those that did develop plague survived markedly longer than animals
vaccinated with a placebo. The scientists believe their plant-based
expression system offers the potential to make high quantities of this
vaccine at relatively low cost. In the United States, the last urban
plague epidemic occurred in Los Angeles in 1924-25. Since then, there
have been mostly scattered cases in rural areas (an average of 10 to 15
persons each year), according to the Centers for Disease Control and
Prevention. Globally, the World Health Organization reports 1,000 to
3,000 cases of plague every year.

SOURCE: Proceedings of the National Academy of Sciences, January 9, 2006.


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