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![]() December 1999 | ![]() |
IN THIS ISSUE:
Food for Thought
Potential Impacts of Pollen from Bt Corn
Molecular Farming Goes Underground
The Good News about Bt Corn
Gene Flow Between Cultivated and Wild Beet
Teaching Plants to Cope with Salt
Hurdles in the Race to Patent New Genes
AgBiotech Debate Impacting Corporate Landscape
Upcoming Meetings

Dear Readers,
Ruth Irwin has been working this year as Associate Editor of the ISB News Report. She has been taking on increasing responsibility for coordinating each issue, editing submitted articles, working with authors to balance accuracy and readability, and cultivating new writers. I am pleased to announce that as of January, 2000, Ruth Irwin will assume the position of Editor of the News Report. I will continue to serve as a sounding board when needed, but will be devoting the majority of my time to activities in international development that are independent of the ISB grant project. Thanks for your continued support of the News Report and all other ISB projects, and as always, keep in touch!
FOOD FOR THOUGHT
`Gene Technology -- Food for Thought' was the title of a conference hosted by
the Consumer Institute of South Africa in October 1999. Although initially dominated
by speakers who cautioned against use of genetically modified (GM) crops, the
conference ended with organizers calling for more public education on GM food issues.
The keynote speakers were Dr. Michael Hansen, from the US Consumers'
Union, and Dr. John Fagan, of the Maharishi University of Management in Fairfield,
Iowa and founder of Genetic ID, a company that tests foods for the presence of
foreign DNA and protein. The two speakers voiced many concerns relative to GM
crops, such as instances of lower than expected yields from herbicide resistant cultivars;
the damaging effects of agricultural monocultures on biodiversity; the influence
of multinational seed companies on countries' economies; and the demise of the
small-scale farmer.
Dr. Fagan argued that the introduction of even a single foreign gene into a plant
could alter that crop's entire metabolic pathways in totally unforeseen ways. Dr.
Hansen stated it was naïve to think that the world could not produce enough food without
GM technology, asserting instead that shortages result from poor food distribution.
In addition, he commented that the segments benefiting from GM foods were the
seed companies and the farmers.
Other speakers, however, espoused different perspectives, indicating that
food distribution in Africa is also hampered by lack of physical
infrastructure, as well as political turmoil and corruption in many
countries. Some participants felt that purported yield increases and the ability
to grow crops in marginal areas, both potential benefits of GM
technology, were essential requirements for feeding Africa's
population. However, it was likewise noted that GM foods are not a "quick
fix" and only part of the long-term solution.
Participants acknowledged that though the first generation of
GM foods do not benefit the consumer directly, second generation
crops currently under investigation should. Rice with higher vitamin
A content, maize with enhanced essential amino acid levels, and
plants with improved oils were some of the examples cited of the next
wave of GM crop attributes.
One speaker, Muffy Koch, Director of Innovation
Biotechnology, spoke of the benefits of planting insect tolerant GM crops.
She emphasized reports of decreased pesticide use, which can result
in increased biodiversity, and noted that a decrease in insect damage
to GM crops may also reduce post-harvest fungal infection, thus
diminishing mycotoxin food contamination, which has been linked
to esophageal cancer in many parts of South Africa. She pointed out
that use of GM crop technology was appropriate for both commercial
and small-scale, resource-poor farmers.
Considerable concern was expressed that multinational
corporations could control agricultural output worldwide through ownership of
plant genome patents, and it was suggested that developing countries
be exempt from patent restrictions. Another concern mentioned was
the exploitation of indigenous plant genomic resources with no
recompense to Africa.
Participants largely agreed that labeling of GM foods was
necessary to allow consumer choice, and acknowledged that the agreement
to label GM food in New Zealand and Australia was not made on
the basis of any recorded public health or safety concerns, but on
consumer information grounds. An allergist, Dr. Harris Steinman,
talked of the fear of unintentionally introducing or creating allergens in
GM foods, pointing out that some allergens are very stable and might
not be destroyed by the cooking process.
Many participants expressed dismay that the GMO Act, passed
in South Africa in 1997, had not yet been implemented. SAGENE
(South African Genetic Experimentation Committee), the former
regulatory body, has been trying to "hold the fort" in the interim. The
Department of Agriculture has indicated that the act will be implemented
before the end of 1999. Until then, all applications for new GM trials
and commercial releases are currently "on hold."
An environmental lawyer, Mariam Mayet, representing Biowatch,
a South African organization opposed to the use of GM food,
stressed the importance of using the precautionary principle, which states that
if there is any scientific uncertainty regarding the possible harm
to human health or the environment, caution must be exercised.
Throughout the course of the meeting, the need for
public education became increasingly clear. However, in a
country such as South Africa in which consumers range from
the illiterate to savvy internet users, education challenges
are extensive. In her summation, Diane Terblanche, the
Chief Executive Officer of the South African Consumer
Institute, pledged her organization's help in the education process,
thus ending the conference with a renewed commitment from
most participants to continue to investigate the advantages
and disadvantages of GM foods.
Jennifer A. Thomson
UPDATE: POTENTIAL IMPACTS OF POLLEN FROM Bt CORN
Scientists convened in Chicago on November 2 to
share preliminary results of research conducted last summer on
the possible effects of genetically engineered Bt corn on
the monarch butterfly.
The Bt toxin found in Bt corn is active against the
Lepidoptera family of moths and butterflies, including the
monarch butterfly. However, when Bt corn was approved in
the US and Canada, regulators and scientists reasoned that
the impact of Bt cornor more correctly the pollen from Bt
corn containing active toxinon monarch populations would
be minimal. This is because milkweed, the desired food
of monarch larvae, is rarely found in corn fields, but in
adjacent fields, and the toxin is rapidly inactivated by ultraviolet
light and drought conditions. They further reasoned that
non-discriminate spraying for other corn pests may present
a significantly higher risk to the monarch population
through chemical drift.
In May 1999, a study by Cornell University
researchers published in the journal Nature (1) indicated that pollen
from Bt corn could kill monarch caterpillars in laboratory
tests. The authors correctly recognized that the study was limited
in applicability, and that field tests would be required to
determine the significance of this finding in an artificial
environment. Upon publication, Dr. John Losey was quoted
as saying, "We can't forget that Bt corn and other
transgenic crops have a huge potential for reducing pesticide use
and increasing yields. This study is just the first step, we need
to do more research and then objectively weigh the risks
versus the benefits of this new technology."
In response to the Cornell report, a consortium of
biotechnology and pesticide companies the Agricultural
Biotechnology Stewardship Working Groupfunded 17 studies
to quantify the risk of Bt corn to monarchs. The research
was conducted during the summer of 1999 at universities in
corn-producing regions of North America. Data presented at
the meeting indicated that not all strains of Bt corn are
equally toxic (2); some varieties of Bt corn may, in a theoretical
or laboratory setting, harm the butterfly, while other types
may not (3). Furthermore, it was suggested that the amount
of pollen migrating to milkweeds was "likely to be dangerous
to only those monarchs feeding on milkweeds within or
close to the edges of the cornfields" (2).
Mark Sears, chair of the Department of
Environmental Biology at the University of Guelph and chair of the
Ontario Corn Borer Coalition, reported that virtually all pollen
grains land within ten yards of the field, 90 per cent of which
travel less than five yards (4). Sears postulated that the risk
to monarch larvae is minimal, especially after discovering
that at least 500 grains of pollen per square centimeter
of milkweed leaf were necessary to sicken caterpillars.
After three days of accumulation during pollination season,
Sears found this concentration was barely attained on
nearby milkweed leaves.
Iowa State University's John Pleasants found that
wind direction, rainfall, and other factors significantly affect
pollen concentrations on milkweed. He reported that,
"Eighty-eight percent of milkweed within one meter of a corn field
would fall below the level where they could hurt the
caterpillars and 100 percent of the milkweed just two meters from a
Bt field would be monarch-safe" (5). Such findings on
pollen dispersion are especially significant when coupled
with planting preferences. Powell et al. (6) found that
planting the borders of a corn field to non-Bt corn was the
second most prevalent implementation of Bt-refugia
guidelines among 400 Ontario corn producers who planted Bt-corn
in 1999, and the most common practice among those
with more than 100 acres of corn.
Brower and Zalucki (2) identified key areas needing
further investigation. The effects of Bt corn on monarch
butterflies will depend on distribution and abundance of
milkweed within and around the edges of corn fields, oviposition on
the milkweeds, and temporal coincidence between
susceptible monarch life stages and pollen shedding of the corn
crop. Review of data indicated basic monarch biology and
ecology were poorly understood, and data from toxicity
bioassays were too preliminary to draw any conclusions. Brower
and Zalucki encouraged researchers to conduct field
research during the summer of 2000, exposing cohorts of monarchs
to pollen on field plants within corn fields using various
Bt strains and non-Bt corn and wild controls. Toxic and
chronic effects of Bt also need to be determined.
Sources
1. Losey JJ, Raynor L, and Cater ME 1999. Transgenic
pollen harms monarch larvae. Nature 399: 214
2. Brower LP and Zalucki MP. 1999. Bt-corn and its effects
on Monarch butterflies: A note of caution. November 11.
e-mail listserve.
3. Currie BM 1999. Altered corn-butterflies.
Associated Press, November 3.
4. Weiss R. 1999. Gene-altered corn's impact reassessed;
studies funded by biotech consortium find little risk to monarch
butterflies. The Washington Post, November 3: A3.
5. Kendall P. 1999. Monarch butterfly so far not imperiled;
gene-altered corn gets an early OK in studies. Chicago
Tribune, November 2: p 4.
6. Powell DA, et al. 1999. A survey of Ontario corn producers
to assess compliance with refugia recommendations to
manage development of resistance to genetically engineered Bt-corn
in the European corn borer, 1999. Agri-food Risk Management
and Communications Technical Report No 10. http://www.oac.uoguelph.ca/riskcomm/plant-ag/bt-survey/bt-survey.htm
Excerpted with permission from Update: Potential Impacts
of Pollen from Bt-Corn. Agri-food Risk Management and
Communication. November 15, 1999. http://www.plant.uoguelph.ca/riskcomm/plant-ag/rc-plant-ag.htm
Douglas Powell
MOLECULAR FARMING GOES UNDERGROUND
Since the advent of plant biotechnology, there has
been much interest in using plants as "green factories" to
produce compounds of industrial or pharmaceutical value.
The advantages seem obviousbesides being easy to grow
and transform, plants are able to perform many of the
protein modifications necessary to produce biologically
active products, unlike many bacteria. In addition, there is a
lower risk of contamination of the end product by infectious
agents, as there is with transgenic animal systems.
Unfortunately, extraction of these recombinant products from plants
often involves multiple, complex steps, which ultimately makes
this approach economically unfeasible. Promising results
from recent reports now suggest that engineering plants to
secrete recombinant proteins from their roots might solve
this problem at least partially.
Plants secrete large amounts of compounds from their
roots during normal growth. Much of this secretion consists of
a complex mix of carbohydrates, but plants are also capable
of excreting significant amounts of protein under
certain conditions, for instance when phosphate is depleted.
However, the amount and variety of proteins released from
plant roots is far less than that found within the plant, so
targeting a protein for release into the growth medium would
automatically represent a significant purification.
This was the basic idea behind "rhizosecretion," a
concept demonstrated by Ilya Raskin and colleagues in two
recent articles in Nature Biotechnology and
Proceedings of the National Academy of
Sciences. Using a strong root promoter, three heterologous proteins of different
originsgreen fluorescent protein (GFP), human placental
secreted acid phosphatase, and bacterial xylanasewere
expressed in tobacco plants grown in liquid culture. The authors
took advantage of a natural phenomenon wherein
proteins targeted to the endoplasmic reticulum (ER), without
additional signaling information, enter a default pathway
leading to secretion. By placing each of the three proteins behind
an ER targeting peptide sequence, they were able to
persuade the plants to excrete the recombinant proteins from
their roots. In all three cases, the secreted proteins retained
their biological activities, resulting in green fluorescent
growth medium in the case of the GFP transformed plants.
Growth of the transgenic plants in liquid culture is key
for taking full advantage of this approach. This process,
known as hydroponics, is a well established method of plant
culture that is far less expensive and labor intensive than cell
or organ culture. In a more conventional approach,
recombinant proteins accumulate within plants, which are then
harvested and the product is purified. With the root expression
method, protein products are being continuously secreted into
the culture medium and thus the harvest can continue over
the course of the plant's lifetime.
There are potential problems of course, even with
this approach. For example, not all proteins will retain
their biological activity through the secretion process and
the excreted proteins may lose their stability in the
culture medium, requiring rapid removal. Additionally, the
normal secretion of carbohydrates and proteins from plant roots
will demand some purification of the recombinant
product, though far less than if expressed internally. The
applicability of this approach to other foreign proteins is also not
clear, especially in the case of mammalian proteins, as there
may be problems expressing and secreting longer peptides
or proteins with unusual modifications.
The technique of rhizosecretion is at an early stage and
the full potential of this method has yet to be demonstrated,
but these initial results from Raskin and his colleagues
show significant promise in making plant production of
recombinant protein economically feasible.
Sources
1. Borisjuk N, et al. 1999. Production of recombinant proteins
in plant root extracts. Nature
Biotechnology 17:466-469.
2. Gleba D, et al. 1999. Use of plant roots for
phytoremediation and molecular farming. Proceedings of the National Academy
of Sciences 96:5973-5977.
Claire Granger
THE GOOD NEWS ABOUT Bt CORN
Recently, non-target effects of Bt corn have become
the subject of a great deal of debate and this debate has
fueled opposition to Bt corn and genetically modified crops
in general. Non-target effects, however, are not all bad. In
fact, we have found that Bt transformation of corn hybrids
can actually enhance their safety as food products because
Bt corn hybrids are significantly less likely to contain
harmful mycotoxins than their non-Bt counterparts.
When insects attack corn plants, one result is an increase
in diseases. This occurs because insect pests carry
pathogenic fungi and predispose plants to disease development.
These diseases include ear rots and stalk rots that can reduce
corn yield and quality. Some of the diseases are caused by
fungi that produce mycotoxins in the corn crop. Mycotoxins,
which are toxic compounds produced by fungi, pose a
significant problem worldwide, affecting an estimated 25% of
grain crops.
The major mycotoxins in corn include aflatoxins,
produced by fungi in the genus Aspergillus, and fumonisins,
produced by several species of Fusarium fungi. Both aflatoxins
and fumonisins can be fatal to livestock and are probable
human carcinogens. The importance of fumonisins in human
health is still a subject of debate, but they are carcinogenic
to laboratory animals and there is evidence that they
contribute to human cancer in some parts of the world.
Fumonisin concentrations in corn are or will be under
regulatory scrutiny in several nations. The economic impact of
aflatoxins has been greater than that of fumonisins because
many nations already have regulations on allowable
aflatoxin concentrations in crops. Symptoms of Fusarium and
Aspergillus ear rots are often highly correlated with
insect damage.
Since 1994, we have been studying the influence of
Bt expression on Fusarium ear rot and fumonisins in corn.
In these studies, differences among types of Bt genes (or
Bt events) have become evident. All Bt events are not
alike. They differ in the specific Bt protein they express and in
the tissue-specific expression of the proteins. Kernel
expression of Bt proteins appears to be an important factor
determining the amount of kernel feeding by European corn borer
larvae and subsequently the intensity of Fusarium infection.
Results of our studies have consistently demonstrated
that hybrids containing two of the Bt events (MON810
and BT11) experience significantly less Fusarium ear rot
and yield corn with lower fumonisin concentrations than
their non-Bt counterparts. Similar results have been obtained
in studies conducted in Illinois and North Carolina (1, 2,
3). When conventional hybrids were subjected to high
populations of European corn borers, Fusarium
ear rot severity and fumonisin concentrations became elevated, often to
levels considered unsafe for swine and horses. Levels
considered safe for horses and swine are <5 ppm and <10 ppm,
respectively. Safe fumonisin levels for humans are unknown
(4). Fusarium ear rot and fumonisin levels in MON810,
CBH351, and BT11 hybrids were uniformly low (usually less than
10% of the concentrations in the non-Bt hybrids) and
were unaffected by European corn borer populations.
Other studies also have shown reduced kernel infection
by A. flavus and lower aflatoxin concentrations in BT11
and MON810 hybrids compared with their non-Bt
counterparts. However, these reductions have been less dramatic
than those seen for fumonisins (5).
Although the results described here support the utility of
Bt hybrids for management of Fusarium and Aspergillus
ear rots and stalk rots of corn, it should be emphasized that
these diseases all require an integrated management
approach involving other tactics. When conditions are very
favorable for disease, protection from insect damage may not
be enough. Another limitation of Bt corn hybrids is their
spectrum of activity. Currently available events are not
effective against the full spectrum of insects that can contribute
to kernel damage and subsequent mycotoxin
contamination.
Future Directions
Bt hybrids can be an important tool in the
integrated management of Fusarium and Aspergillus ear rots. New
Bt hybrids now under development promise to exhibit
more complete control of other kernel-feeding insects, so
they should provide even better protection from
insect-associated fungi, and there could be further contributions
toward mycotoxin management. Transgenic control of insects
and diseases offers an alternative that is much more
effective, consistent, economical, and environmentally sound
than foliar insecticides.
Debate surrounding the use of genetically modified
crops should be based on an assessment of all risks and
benefits that can be measured, including environmental
impacts, livestock impacts, and potential human health
threats. Available data show that Bt transformation of corn
hybrids enhances the food and feed safety of the grain by
reducing its vulnerability to mycotoxin-producing fungi. A
common criticism of currently available genetically modified crops
is a lack of apparent benefits to consumers. But
lower mycotoxin concentrations represent a clear benefit
to consumers of Bt grain, whether the intended use is
for livestock or human food products. Consumers and
regulatory agencies should consider these factors in
decisions regarding Bt corn use.
Sources
1. Dowd PF and Munkvold GP. 1999. Associations
between insect damage and fumonisin derived from field-based
insect control strategies. Proceedings of the. 40th Annual Corn
Dry Milling Conference, June 3-4, 1999. Peoria, IL.
2. LSI Health and Environmental Sciences Institute. 1999.
An evaluation of insect resistance management in Bt field corn:
A science-based framework for risk assessment and risk
management. Washington, DC: ILSI Press.
3. Munkvold GP, Hellmich RL, and Rice LG 1999. Comparison
of fumonisin concentrations in kernels of transgenic Bt
maize hybrids and non-transgenic hybrids. Plant
Diseases 83:130-138.
4. Munkvold GP, and Desjardins AE. 1997. Fumonisins in
maize: Can we reduce their occurrence? Plant
Diseases 81:556-565.
5. Windham GL, Williams WP, and Davis FM. 1999. Effects of
the southwestern corn borer on Aspergillus
flavus kernel infection and aflatoxin accumulation in maize hybrids.
Plant Diseases 83:535-540.
Gary P. Munkvold
Richard L. Hellmich
GENE FLOW BETWEEN CULTIVATED AND WILD BEET
The genetic modification of crops has drawn criticism
from opponents who contend that gene flow from these
crops may endanger wild populations of sexually compatible
weedy relatives. In a study published recently in
Molecular Ecology, Detlef Bartsch and Norman Ellstrand have reported
the feasibility of gene flow between cultivated and wild beet
(1). Their model for this study was Beta
vulgaris, a species that includes internationally grown crops of red beet, sugar
beet, and Swiss chard.
Beet has been grown since the third century AD, but had
not been cultivated into domesticated varieties until the 1800's
in Germany and France. Cultivated varieties of beet in
the Chenopodiaceae family are grown widely for
human consumption, the production of sugar, and for
livestock fodder. The family is also noted for containing many
invasive weed species affecting agricultural fields.
To show the impact of gene flow from cultivated to
wild populations, Bartsch and Ellstrand tracked the frequency
of isozyme alleles commonly found in cultivated
Beta vulgaris and in the wildtype sea beet
(B. maritima). They studied agricultural conditions in which naturally occurring
weedy relatives are grown near stands of the cultivated crop.
Ellstrand's group quantified isozyme alleles specific to
the cultivated beet. These alleles appeared in high frequencies
in the 26 study accessions of the crops. Although
isozyme genes are rarely found in wild sea beet populations, the
20 sea beet accessions growing near cultivated beet
varieties contained isozyme alleles at a level characteristic of
that found in cultivated plants. These gene frequencies were
not found in the 19 sea beet accessions growing in isolation
from the cultivated beet crops.
The Bartsch, Clegg, and Ellstrand research team
has conducted extensive studies on beet genetic
divergence using allozyme analysis, as well as gene flow studies of
other crop plants. Although this study did not show the
direct transmission of the genes from the cultivated crop to the
wild plants, it supports a 1992 study by S. Santoni and A.
Berville that reported the successful sexual reproduction
between cultivated and wild beet (2). At the conclusion of their
study, Santoni and Berville warned that sexual compatibility
could likely be a possible mechanism of gene transmission
between transgenic and wild beet. Similarly, a 1998 study
indicated that isozyme variations most likely occur by gene
exchange and not random variation (3).
Bartsch and Ellstrand suggest that gene flow is a
potentially important driving force in plant evolution, and their
research demonstrates gene flow rates that are higher than
previously anticipated between different populations of plants. They
are concerned about the evolutionary consequences of
gene hybridization between crops and wild relatives.
Their concerns echo those expressed by K. Morgan and
C. Strobeck in their 1979 paper in Nature in which they
identified many of the issues associated with intragenic
recombination and the genetic stability of natural populations (4).
Gene flow from GM crops is important because of
the possibility that novel genes could have deleterious effects
on the wild plant populations. However, a century of
conventional gene flow has had no adverse effect on the
genetic diversity of wild sea beet populations in Italy. The impact
of transgenic gene flow will depend on the ecological
advantage of the trait. As recently demonstrated by Bartsch
and his collaborators, transgenically introduced resistance to
a serious viral disease called Rizomania in cultivated beet
will have no adverse effect on wild sea beet populations,
because the virus is not present in this group (5). The effect
of other fitness enhancing traits on wild beet populations
may differ, but it is absolutely case dependent.
Recently, the beet has received much publicity because
of the development of the GM sugar-free beet
(genetically modified to convert sucrose to fructan) in the
Netherlands, and Monsanto's high-sucrose beet. GM beet field trial
sites have been the target of vandalism in 1995 and 1996
in Germany, and 1997 and 1998, respectively, in Ireland
and England. A glyphosate-tolerant sugar beet has recently
been deregulated in the US as well. GM technology opponents
are using scientific findings, such as the Bartsch
and Ellstrand study, to legally combat the release of GM crops.
Sources
1. Bartsch D, Lehnen M, Clegg J, Pohl-Orf M, Schuphan I,
and Ellstrand NC. 1999. Impact of gene flow from cultivated beet
on genetic diversity of wild sea beet populations.
Molecular Ecology 8(11):1733-1741.
2. Santoni S and Berville A. 1992. Extramarital sex amongst
the beetsevidence for gene exchanges between sugar beet
(Beta vulgaris L.) and wild beets: Consequences for transgenic
sugar beets. Plant Molecular Biology 20(4):578-580.
3. Tufto J, Raybould AF, Hindar K, and Engen S. 1998.
Analysis of genetic structure and dispersal patterns in a population of
sea beets. Genetics 149(4):1975-1985.
4. Morgan K and Strobeck C. 1979. Is intragenic recombination
a factor in the maintenance of genetic variation in natural
populations? Nature 227(5696):383-384.
5. Bartsch D, Schmidt M, Pohl-Orf M, Haag C, and Schuphan I.
1996. Competitiveness of transgenic sugar beet resistant to
beet necrotic yellow vain virus and potential impact on wild
beet populations. Molecular Ecology 5:199-205. Brian R. Shmaefsky
TEACHING PLANTS TO COPE WITH SALT
University of Toronto scientists have isolated a critical
gene responsible for salt tolerance in plants that may
eventually help them grow crops using salt water. The salt
tolerance gene, isolated from the
Arabidopsis plant, encodes a transport protein in plant cells whose activity enables
plants to grow under highly saline conditions.
Salinity is a major abiotic stress limiting the productivity
of crop plants around the world, especially under
irrigated conditions. Rice soils, which are mostly irrigated,
are declining in productivity in many Asian countries
because of increasing salinity levels. It is estimated that 25
million hectares (62 million acres) of agricultural land in the
world suffers from excess salinization, and another two
million hectares of salinated land are added each year.
The presence of excess salt in soil is doubly harmful
for plants: salt increases osmotic pressure in plant
tissues, resulting in water stress; and sodium ions harm plant
cells directly by interfering with plant metabolism. Ensuring
an increase in agricultural productivity, especially in
the developing countries, hinges on the capacity to sustain
crop production on marginal lands afflicted with salinity
and water stress factors.
Plants that have adapted to high salt conditions often
have done so by shuttling sodium into vacuoles within the
plant cell. This compartmentalization prevents sodium ions
from harming the plant cell and provides a proper
osmotic balance for plant cell water uptake. A Toronto group,
led by Eduardo Blumwald, suspected that compartmentation
of sodium ion into vacuoles may be mediated by the
transport protein, Na+/H+ antiport. As many genes from
diverse organisms share similar nucleotide sequences, the
Toronto group used the DNA sequence of a yeast gene for
this antiport protein to search the
Arabidopsis genome database. Fortunately, a corresponding gene for the
antiport protein called AtNHX was detected.
The group then over-expressed
this gene in Arabidopsis using a highly efficient
"supermas" promoter (see "New `super-promoter' drives very
high expression of introduced genes in plants," ISB
News Report, June 1996).
As predicted, transgenic plants overproducing the
Na+/H+ antiport protein were highly tolerant of saline
conditions. While wild-type plants were stunted, turned chlorotic,
and had smaller leaves when watered with a nutrient
solution containing increasing salt concentrations, the
transgenic plants with the AtNHX gene grew well in soil irrigated
with up to 200 millimolar salt water, and set seed normally.
This increased salinity tolerance in transgenic plants was
correlated with higher-than-normal levels of
AtNHX transcripts and an increased activity of Na+/H+ antiport in vacuoles.
As most plants have low antiport activity, they
cannot adapt to increasing salinity conditions; consequently,
these plants lose water, grow slowly, and ultimately die.
The overproduction of the antiport protein in the model
plant Arabidopsis shows that it is possible to redesign
crop plants to help them endure saline conditions and still
remain productive. "By successfully genetically engineering a
plant to have this salt management system, we've opened up
the possibility of modifying economically important crops
so that they may grow in saline conditions," says Blumwald.
Source
Apse MP, Aharon GS, Snedden WA, and Blumwald E. 1999.
Salt tolerance conferred by overexpression of a vacuolar
Na+/H+ antiport in Arabidopsis. Science
285, 1256-1258.
C. S. Prakash
HURDLES IN THE RACE TO PATENT NEW GENES
President Bill Clinton and Prime Minister Tony Blair
are reportedly in the midst of formalizing the Bermuda
Accord, a plan to ensure that the UK-owned Wellcome Trust
and the US National Institutes of Health make each
gene sequence public within 24 hours of discovery.
Their objective is to hinder the race to patent human genes
by rapidly creating prior art.
Prior Art Slalom: New Means New
The reasoning behind the novelty requirement is that
a patent should not remove something from the
public domain. This policy is also reflected in the fact that
a patent should not issue for a claimed invention that
would have been an obvious variation of something in the
public domain at the time the invention was made. How can
a gene be obvious?
Prior Art Slalom: New Means Structurally Nonobvious
This structural obviousness approach to examination
of genes is similar to the method that US patent
examiners and courts have used to determine the obviousness
of simple chemical compounds. Not all patent offices,
however, embrace the concept of structural obviousness
for claimed genes. At present, the Japanese Patent
Office appears to use an approach to determine
nonobviousness, or "inventive step," similar to the analysis used in the
US before the 1993 Federal Circuit decision. An inventive
step inquiry that focuses on whether one
could have isolated a gene using standard techniques tends to render
genes unpatentable as gene isolation technology advances.
Steeplechase: The Sufficiency of Disclosure
The "how-to-make" requirement should not present
a serious obstacle for a claimed gene if the patent
application discloses the nucleotide sequence or the amino
acid sequence of the encoded protein. The
"how-to-use" requirement also should not pose a notable barrier, so
long as the application includes some discussion about use,
or the patent examiner finds the use intuitively obvious. It
is better to rely upon the former than the latter.
The patent office and the courts usually view the
how-to-use requirement differently for a claim to a gene and
a claim to a method of using the gene. For example, a
patent examiner should not force a patent applicant to prove
that claimed antisense polygalacturonase DNA
constructs inhibit gene expression, because those constructs are
also useful for the simple task of detecting
polygalacturonase mRNA. However, the burden for supporting a claim to
an antisense method can be significant. This is a lesson
that Enzo Biochem Inc. discovered during an
infringement action against Calgene Inc.
In this case, Enzo, the exclusive licensee of patents
claiming general methods for using antisense technology,
alleged that the FLAVR SAVR tomato infringed its
patents. Following a bench trial, a Delaware district court
concluded that the relevant patent claims were invalid because
the specification failed to disclose the how-to-use aspect of
the enablement requirement. Recently, the Federal
Circuit affirmed the decision, explaining that the technology
was highly unpredictable at the time of patent application
filing, and that a high degree of experimentation was required
to adapt the patents' disclosed methods for using antisense
in E. coli to other types of cells (2).
The best mode requirement is related to enablement. In
the US, a patent application must set forth the best
mode contemplated by the inventor for carrying out the
invention. Monsanto and others argued, albeit unsuccessfully,
that Mycogen's inventors had failed to comply with the
best mode requirement by not disclosing the best form of
a synthetic Bt gene in their patent applications (3).
Hare and Hounds: Clues about the Written
Description Requirement
In recent years, the Federal Circuit has shown a
tendency to limit claim scope to particularly disclosed
embodiments of the invention. This is exemplified by
UC v. Lilly in which the court explained how the written description
requirement is applied to claimed genes. Here, the court determined
that a patent disclosure of a general method for
producing human insulin cDNA and a description of human
insulin amino acid sequences failed to provide a written
description of human insulin cDNA (4). The court emphasized
that the question of whether the patent truly described how
to obtain the human insulin gene was not relevant to
the written description analysis. Instead, the analysis hinged
on the sufficiency of nucleotide sequence disclosure in
the patent application.
So, how much information must a patent application
contain to meet the written description requirement for a
claimed gene? A conservative answer is that the patent
application should include sequences for all variations that the
inventor wishes to claim.
The PTO has been struggling with the Federal
Circuit's written description requirement for genes, issuing one
set of proposed guidelines last year and another set by the
end of this year. Perhaps, the PTO will devise a less
burdensome approach that will win the approval of the courts.
Sources
1. In re Bell, 26 USPQ2d 1529. 1993. Federal Circuit.;
In Re Deuel, 34 USPQ2d 1210, 1215. 1995. Fed. Cir.
2. Enzo Biochem Inc. v. Calgene Inc., 52 USPQ2d 1129. 1999.
Fed Cir.
3. Mycogen Plant Science Inc., et al. v. Monsanto Company,
et al., Civil Action No. 96-505-RRM. 1999. D. Del.
4. The Regents of the University of California v. Eli Lilly
and Company, 43 USPQ2d 1398. 1997. Fed Cir.
Phillip B. C. Jones, PhD., J.D.
AGBIOTECH DEBATE IMPACTING CORPORATE LANDSCAPE
The debate over the merits of agricultural
biotechnology has found a growing audience in the American media.
The Biotechnology Industry Organization (BIO) has tracked
a significant increase in the level of media interest in
biotechnology over the past year, driven mostly by
Congressional debate over Medicare issues and the controversy
over agricultural biotechnology (1).
How much of this "expanded" coverage is due to
the media's thirst for a good story and how much is
tangible public concern is yet to be determined. A Gallup Poll
taken as recently as September of this year revealed that
only slightly over one-quarter of Americans believe that
genetically modified foods pose a serious health hazard
to consumers. The press release noted that " . . .
Americans today seem quite relaxed about food safety issues" (1).
Whereas this data suggests that Americans may not be
as concerned about agbiotech safety as some in the
media would suggest, Wall Street and major corporate players
are not convinced.
A major indicator of the financial and corporate
communities' inability to gauge the future of the public's response
to commercial agricultural biotechnology is the
performance of Monsanto's stock. The stock has not performed at
the level expected and a number of Wall Street analysts
are calling for the St. Louis-based company to split the
company into parts, separating its pharmaceutical business
(the G.D. Searle unit) from the crop-biotechnology business.
Some feel that Monsanto's stock price is placing little to
no value on the crop-biotechnology business. At times
within recent weeks, Monsanto's stock price has put a
market value on the Company of about $24 billion. Some
analysts believe that the value of the Searle drug unit alone could
be upwards of $25 billion, and that a sell off of
Monsanto's parts could yield at least a 30 percent premium over
the value currently being placed on the company by the
public markets. Recent merger activity in the
pharmaceutical sector has started to drive Monsanto's stock up, but
there is still pressure on the Company's management to
do something to bolster the stock's performance (2).
In response, Monsanto has been holding discussions
with rivals regarding a possible merger. As of the writing of
this article, Novartis was being mentioned as the most
serious potential suitor, but word has it that other companies
have met with Monsanto to discuss options, including
Schering-Plough, DuPont, and Pfizer. Novartis is getting the
most attention given that it has substantial businesses in both
the pharmaceutical and agricultural arenas, thus offering
a good fit with Monsanto. One possibility that has
been mentioned is the combination of the two
companies' agrochemcial businesses and formation of either a
spin-off of that entity or the issuance of a tracking stock.
This scenario would be driven largely by the uncertainty
currently surrounding the agricultural sector and would
allow investors to put their money into the
pharmaceutical business independent of the crop-biotechnology
business (3).
Adding to uncertainty of the investment and
corporate communities surrounding commercial agricultural
biotechnology is the impact of the continued controversy
in Europe. The United States has lost an approximated
$200 million in European corn sales alone over the past
few years because of delays in the European Union
approval process for genetically modified crops (4). Other
negative factors impacting commercial agriculture in general
in recent months include reduced government subsidies
to farmers and depressed commodity prices, both part of
a cyclical downturn in the industry (5).
Jointly, all of these factors have caused some on
Wall Street to question if the rate of return on the huge
investments that many agrochemical companies have made
in the last few years in new biotechnologies will be
adequate. Others believe that this type of debate is inevitable
as applications of biotechnology continue to make their way
to the dinner table, and that the technology still holds the
most promise to add value to commercial agriculture. In
either case, it appears that corporate players in agricultural
biotechnology have brought some of this on themselves by
under-investing in public education, and, in turn, putting a
premium on the media's role in helping to shape public perceptions
and adding to the uncertainty surrounding an already
controversial topic.
Sources
1. Vogt W. Consumer acceptance key to biotech crop growth.
Oct/Nov 1999. BIO News, 4.
2. Kilman S, and Burton TM. Monsanto faces pressure
to break up the Company. Oct. 21, 1999. The Wall Street Journal
Interactive Edition, (http://wsj.com).
3. Deogun N and Burton TM. Monsanto considers full or
partial sale; Novartis is a suitor, pact isn't imminent. Nov. 9, 1999.
The Wall Street Journal Interactive Edition, (http://wsj.com).
4. Palmer D. FOCUS - U.S. pursues two-track biotech
crop strategy. Nov. 9, 1999. Reuters, (retrieved from
http://biz.yahoo.com/rf/991109/bp2.html).
5. Moore SD. Novartis plans to slash 1,100 jobs in overhaul
of agrochemical unit. June 23, 1999. The Wall Street Journal
Interactive Edition, (http://wsj.com).
William O. Bullock
ABIC 2000
ABIC 2000 will explore the many opportunities
agricultural biotechnology offers the world through scientific
breakthroughs, commercial developments, and technology
transfer. The Conference Program presents the latest in
agbiotech science, business, and education, and features
internationally recognized speakers including Dr. Barry
Greengrass of UPOV/WIPO, Dr. Terry Medley of DuPont USA,
Ms. Sylvia Rowe from the International Food Council (IFC),
Mr. Sano Shimoda of BioSciences Securities Inc.,
and Dr. Maria Zimmermann from the FAO.
Contact:
Australian Biotechnology Conference: ABA2000
The theme of the conference, "Biotechnology:
Our passport to the next millennium," reflects the opportunities that
the revolution in the life sciences will provide for all sectors
of society, and the equal importance of engaging all sectors
of society in these opportunities. The four main themes
are Food and Fibre Biotechnology; Pharmaceutical
Biotechnology; Environmental and Marine Biotechnology; and
Bio-business.
Contact:
6th International Symposium on the Biosafety of Genetically Modified Organisms
Approximately 70 invited internationally recognized
experts will address the scientific basis for biosafety
(environmental as well as human and animal health issues) associated
with genetically modified organisms. The information
presented and discussion generated at this meeting will influence
the development of a "science-based" regulatory policy
governing the release of Genetically Modified Organisms
(GMOs). The Symposia series is designed for senior scientists,
policy makers, regulators, environmentalists, and industry
representatives involved in the commercial release of GMOs.
Contact:
ISB News Report
The material in this News Report is compiled by NBIAP's Information Systems for Biotechnology, a joint project of USDA/CSREES and the Virginia Polytechnic Institute and State University. It does not necessarily reflect the views of the U.S. Department of Agriculture or of Virginia Tech. The News Report may be freely photocopied or otherwise distributed without charge.
To have the News Report automatically emailed to you, send an email message to
news@nbiap.biochem.vt.edu
and type subscribe newsreport [your_name] in the message section. Do not include a signature file or additional text.
Connect to http://www.isb.vt.edu for internet access to ISB News Reports, textfiles, and databases.
Information Systems for Biotechnology, 120 Engel Hall, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, tel: 540-231-2620, fax: 540-231-2614, email:
isb@vt.edu
Department of Microbiology
University of Cape Town
jat@molbiol.uct.ac.za
Dept. of Plant Agriculture
University of Guelph
dpowell@uoguelph.ca

Carnegie Institution of Washington
Department of Plant Biology
claire@Andrew2.Stanford.edu
Department of Plant Pathology
Iowa State University
munkvold@iastate.edu
USDA-ARS Corn Insects and Crop Genetics
Research Laboratory & Iowa State University
rlhellmi@iastate.edu
Department of Biology and Environmental Sciences
Kingwood College, Kingwood, TX
bshmaefs@nhmccd.edu
Center for Plant Biotechnology Research
Tuskegee University
prakash@tusk.edu

A gene, like any other subject of a patent application,
must meet various statutory requirements, including the
requirement of novelty. To be novel, an invention must differ
from the prior art, which is the sum of publicly available
information. A nucleotide sequence, published on an
Internet database, will prevent a patent applicant from obtaining
a patent for the nucleotide sequence in a subsequently
filed patent application. Under US patent law, an exception
to this rule would arise if the patent applicant
subsequently files a patent application and can prove a date of
invention within one year of the Internet publication.
There was a time when the US Patent and
Trademark Office (PTO) viewed an isolated gene as obvious in light
of a reference that describes a related gene (such as
a homologous gene) and a standard text of molecular
biology protocols. However, in 1993, the Court of Appeals for
the Federal Circuit made it clear that a case of
obviousness requires that the prior art discloses a gene related to
the claimed gene and a suggestion in the prior art to modify
the known gene to obtain the claimed gene (1).
US patent law also imposes requirements for the content
of the patent application. For example, a patent
application must contain a sufficiently detailed description of
the invention to enable others to make and use the
invention without "undue experimentation." Although routine
experimentation to reproduce an invention is acceptable,
the degree of experimentation must not be burdensome
when viewed in light of the particular area of technology
involved and the level of skill in that field of technology.
US patent law also imposes a written description
requirement, which requires that the patent application
evidences that the inventor had possessed the claimed invention
when the application was filed. In the case of a specific
nucleotide sequence, the written description requirement can
be fulfilled by disclosing that nucleotide sequence.
However, inventors typically want broader claims to prevent
others from avoiding infringement by introducing minor
changes into the nucleotide sequence. Consider claim scope as
a dartboard. If you are forced to narrow claim scope
toward the center, then more room is created for others to
maneuver around you.
Seattle, Washington
pbcj@wolfenet.com

Institute for Biotechnology Information
Research Triangle Park, NC.
wbullock@mindspring.com

More meetings can be found at http://www.isb.vt.edu
Agbiotech: The Science of a New Century
June 5-8, 2000
Sharon Murray
tel: 1-877-925-2242 (N. Am.), 306-934-1772
fax: 1-877-333-2242 (N. Am.), 306-664-6615
http://www.lights.com/abic/

July 2 - 6, 2000
Brisbane, Australia
ABA2000 Secretariat
tel: + 61 (0) 7 3369 0477 / fax: + 61 (0) 7 3369 1512
email: aba2000@im.com.au
http://www.aba2000.im.com.au

July 8-13, 2000
Saskatoon, Saskatchewan Canada
BioSafety 2000
http://www.usask.ca/agriculture/biosafety/index.html

120 Engel Hall
Virginia Tech
Blacksburg, VA 24061