GENTECH archive 8.96-97


ISB Monthly News Report - January 1997

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Subject: ISB Monthly News Report - January 1997
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                   ISB News Report - January 1997

In This Issue:

 -  Insect Control in Agriculture: Report from the ESA Meeting=20
 -  Inventors: Don't Trip over Electronic Timelines
 -  Reflections on 1996
 -  Towards the Development of Cold Tolerant Plants
 -  Edible Plant Vaccines
 -  Transgenic Arthropods: Current Status, Future Prospects
 -  EPA Oversight of Plant-Pesticides
 -  Requirements for Select Infectious and Toxic Agents
 -  State Of the Industry
 -  Trends in Potato Production: Impact of Transgenic Virus



The Entomological Society of America annual meeting in December had
several sessions of interest to the biotech community. The
symposium on "Biotechnology and Agriculture: New Green Revolution
or Recipe for Disaster," was standing-room-only for the entire
morning. A few highlights are given here.

Bt Cotton
Preliminary 1996 performance reports for commercial cotton and corn
varieties genetically engineered with Bt insect control genes were
positive. More than 1.8 million acres of cotton resistant to
bollworm, tobacco budworm and pink bollworm were planted in 1996.
>From the outset, genetically engineered varieties were in high
demand from farmers willing to pay the $32/acre technology fee. As
much as 77% of the cotton acreage in Alabama was planted to Bt
varieties such as DeltaPine Land Company's NuCOTN lines. It was a
good year for cotton throughout most of the southern growing
regions. NuCOTN33B posted an 8-10% increase in yield over its
parental line, due to the combined effects of the Bt insect control
gene and the variety's improved agronomic performance.=20

As with other agricultural products, DeltaPine Land Co. is working
with farmers to optimize performance. In some cases, growers are
advised that transgenic technology may not be the most appropriate
to their particular situation. In other cases, growers must deal
with associated traits that affect harvestable yield. In cotton,
for example, plants should not be too tall. The indeterminate
growth pattern of parental line 33, however, shows up in NuCOTN33B
as a tendency to produce "buggy whip" shoots, which are excessively
tall and have only a few bolls. The company will be advising
farmers on management practices to control this undesirable trait.=20

The first year of introduction has also taught the company a basic
lesson in technology adoption. After determining that half of their
on-farm calls this season were due to farmers getting seed mixed
up, DeltaPine Land Co. began color coding their cotton seeds so
that farmers can better track which fields are planted to
transgenic varieties. A company spokesman estimated that within
five years, 80-90% of cotton seed planted in the U.S. will be

Bt Corn
Did Bt corn resistant to European corn borer deliver on its
marketing promise? This year  transgenic Northrup King lines
produced anywhere from five to twelve bushels per acre more than
unprotected varieties. The Bt gene itself does not confer a yield
advantage, rather it protects the crop's yield potential. In a year
of high insect pressure like 1996, farmers get a high benefit from
Bt varieties, but in a year of low insect pressure the yield
improvement over conventional varieties may only just cover the
added cost. Insect pressures cycle over time and geographical
areas. The U.S. corn belt is coming off two years of high European
corn borer pressure, so while Bt corn did well enough this year to
convince farmers to buy it next year, insect pressure is likely to
decline somewhat. Before they plant their 1997 crop, farmers will
try to predict how serious pest problems will be in the coming
season. Many are expected to decide to pay the $7.50 per acre
premium for Bt seed corn as a form of insurance against next year's
uncertain losses.=20

Engineered Baculoviruses
Insect-specific viruses are being engineered with a variety of
genes to make them more effective biocontrol agents. Genes encoding
diuretic hormone, juvenile hormone, Bt delta endotoxins, and mite
toxins are being added to baculoviruses to improve the killing
power of these viral insecticides.=20

This year's field tests of a baculovirus engineered with the AaIT
gene encoding a scorpion toxin provide a glimpse at the
environmental fate and genetic competitiveness of the recombinant
virus. The tests evaluated the efficacy of genetically-altered
viruses against lepidopteran species (cabbage looper and tobacco
budworm) on tobacco, cotton and leafy vegetables. No difference was
seen in the physical properties of transgenic versus non-transgenic
strains; they were equally sensitive to rapid degradation in
sunlight, slow degradation at temperatures above 85=F8F, and
temperature/moisture interactions.=20

Tobacco budworm larvae killed by the AaIT strain harbored ten-fold
fewer viral inclusion bodies than larvae killed by the non-
engineered strain. This result was expected, since insertion of the
toxin gene leads to faster death of the insect host, therefore
fewer viral progeny are formed. In mixed infections established
with a 9:1 ratio of transgenic to nontransgenic virus, the inserted
gene could not be detected by the 6th generation due to reduced

Use of engineered viral insecticides offers several environmental
benefits. The virus serves as an efficient dose delivery system in
that no toxin is applied to the crop, only the toxin gene. Only in
suitable insect hosts is the toxin gene expressed; when just enough
toxin is produced to kill the host, the system shuts down. The AaIT
toxin binds with high affinity to insect neurons, thus death is due
to disruption of the nervous system rather than from massive viral
infection. While crude scorpion venom does have effects on spiders,
crustaceans and mice, the purified AaIT toxin protein does not. The
toxin has no affinity to mammalian neurons, and neither the toxin
nor the recombinant virus has any clinical effect on nontarget
insects, rodents and beneficial species. Eventually, these data may
help support a food use registration for similar viral pesticides.

More Options
Ciba-Geigy is working with a new class of insect control proteins
produced by Bacillus thuringiensis. Unlike the sporulation-specific
delta endotoxins found as crystals in Bt spores, Vegetative
Insecticidal Proteins are produced during log phase of growth and
secreted. Like the endotoxins, these novel proteins target midgut
epithelial cells, however they have a different activity spectrum.
The effort to discover and develop a wider array of insect control
proteins has dual benefits. If successful, it sidesteps the
increasingly litigious battle over rights to the various Cry genes.
>From an environmental perspective, in broadening the biological
arsenal used to control insects, the threat of pests becoming
resistant to a single over-used compound is lessened.=20

Pat Traynor
Information Systems for Biotechnology


Last October, Science Online began posting full-text articles on
its web site. Such rapid access to new research findings should
enhance the progress of individual projects. On the negative side,
rapid electronic publication can unintentionally create "prior art"
that may bar patent protection for the scientific discoveries
described by an electronically published report.=20

In patent law, prior art is the information used to judge whether
an invention is both novel and nonobvious. In other words, prior
art provides a standard to determine if an invention meets the
legal requirements of a patentable invention. The policy behind the
criteria of novelty and nonobviousness is that a patent should not
remove something from the public domain that either exists as the
claimed invention or exists as an obvious variation of the claimed
invention. Consequently, an invention is not patentable if it was
placed in the public domain before a "critical date." In the United
States, the critical date is the date of invention under 35 U.S.C.
Section 102(a), or one year before the patent application filing
date under 35 U.S.C. Section 102(b).

The present test for determining whether any disclosure is prior
art focuses on the accessibility of information rather than on the
form of the disclosed information. The Court of Appeals for the
Federal Circuit has stated that public accessibility is the
"touchstone" in determining whether a reference constitutes a
"printed publication" form of prior art (1). Therefore, the fact
that a reference is printed electronically, rather than on paper,
is relevant to the prior art determination only to the extent that
publication in an electronic form may affect public availability.
There is little doubt that information posted on a web site is
"effectively part of the public domain, impossible to retrieve"

The bottom line is that the description of an invention in an
Internet electronic publication will initiate the countdown toward
the one-year statutory bar to a U.S. patent. At the same time,
patent rights outside the U.S. may be destroyed at the time that an
invention is disclosed in an electronic publication before filing
a patent application. This is so, because the one-year "grace
period" for publication under 35 U.S.C. Section 102(b) is unique to
U.S. patent practice. =20

It is not possible to overemphasize the importance of knowing the
exact date that an article will be published on the Internet.
Science, for example, posts information online on the same day that
the corresponding paper version is mailed to print subscribers.
This electronic publication advances the effective publication date
of disclosure since, under U.S. patent law, a paper journal is
effective as prior art on the date that it reaches the addressee,
not on the date of mailing (3).

Other online journals publish abstracts or full texts of articles
weeks before the publication date of the paper journal. Under an
enlightened editorial policy, Blood Cells, Molecules & Diseases
informs researchers in its "Instructions to Authors" about the
relative timing of Internet and paper publication. The journal also
includes the Internet posting date on each paper article as the
official date of publication. According to Dr. Ernest Beutler, the
editor-in-chief of Blood Cells, Molecules & Diseases, the reason
that his journal "adopted the practice of accurately dating all of
our articles is precisely to establish priorities both from the
point of view of scientific credit and from the point of view of
establishing a date of dissemination of the intellectual property"
(4). Unfortunately, not all online journals advertise their
relative dates of electronic and paper publication, and it may be
necessary to contact the editorial office of a journal to discover
its publication policies.

Another form of electronic publication that can destroy patent
rights is a nucleotide or amino acid sequence stored in a publicly
accessible database. In fact, public access of such information can
predate both electronic and paper publications of the relevant
research report. Examiners in the European Patent Office have
routinely cited as prior art nucleotide and amino acid sequences
obtained from electronic databases. During the past year, it became
clear that U.S. Patent Office examiners have enthusiastically
adopted this practice as well.=20

In sum, the important point is that under patent law, "publication"
means that information becomes publicly accessible regardless of
the form of the information. With this thought in mind, an inventor
can provide current information to further open scientific
communication, while maintaining a flow of funding.

(1) In re Hall, 228 USPQ  453, 455 (Fed. Cir. 1986).
(2) Religious Technology Center v. Lerma, 908 F.Supp. 1362, 1368
    (E.D.Va. 1995).
(3) Carella v. Starlight Archery, 231 USPQ 644, 647 (Fed. Cir.
(4) Personal communication.

Phill Jones
Foley & Lardner, Madison, Wisconsin


1. In the business arena, 1996 was an active year for
'buyotechnology'. The consolidation of the maturing agbiotech
sector through mergers, buyouts, newly-issued patents and licensing
agreements leaves only a handful of companies at the top tier.
Public research institutions, including land grant universities,
are now adjusting to this consolidation of commercial power and
intellectual property. Their options include negotiating license
agreements with companies, or shifting university research away
from applied biotechnology, or generating alternative tools and
procedures to enable continued applied research.  Another option
may be for public universities to join together in some type of
confederation that gives members easier access to each other's
intellectual property.

2. Consumer concern resurfaced over the transfer of an allergen
from Brazil nut to soybeans, resulting from the transfer of a gene
between the two crops. This result was announced in 1994, and
Pioneer Hybrid stopped further development of that line of
soybeans. That this case made news in 1996 demonstrates the
durability of the issue of allergens and gene transfer. It also
poses an interesting question: should transferred genes be from
sources regarded as highly allergenic (such as legumes), moderately
allergenic, or weakly allergenic? At first, the use of weakly
allergenic donor organisms seems the wiser choice. Some would argue
that using highly allergenic sources has an advantage in that the
allergenicity of the engineered crop can be easily tested. The
obvious response, however, is that the potential to transfer genes
encoding allergenic proteins is a recognized factor to be evaluated
long before consumers ever see the product. In fact, the topic is
explicitly addressed in the FDA's policy on biotech foods.

3. Another example that all news is not necessarily new was the
announcement that a marker gene introduced into canola was
transferred by pollen to weedy relatives. The observation confirmed
that genes flow between canola and weedy relatives, a fact
previously established using conventional marker genes from canola.
However, the perceived risk and tightness of scrutiny applied to
crops genetically engineered with one or two transgenes continues
to be greater than that associated with new cultivars developed by
wide crosses within a genus using conventional means.

4. While 1996 was not the first season genetically engineered
commodity crops such as corn, soybeans, potatoes, and cotton were
commercially grown, it will be remembered as the year that the
issue of fungibility and biotechnology hit international trade and
politics. The term fungibility roughly means that equivalent items
can be substituted or interchanged in fulfillment of a contract.
Does a person who agrees to purchase a metric ton of soybeans
retain the right to refuse a shipment if it contains some soybeans
that are genetically engineered? In October, groups in Europe and
North America announced a boycott against transgenic commodities.
However, in mid December the European Union announced that it would
accept genetically engineered corn; in April the EU had approved
import of genetically engineered soybeans.

Tom Zinnen
Biotechnology Education
University of Wisconsin Biotechnology Center and UW-Extension



Any farmer or home gardener in the temperate region well knows one
cold fact about the winter: freezing temperatures can kill most
plants. Cold temperatures are a major environmental constraint in
crop productivity in these areas. Classical plant breeding has had
limited success in imparting cold hardiness to crop plants, in part
because little is understood as to why some species withstand cold
better than others. Use of biotechnology to isolate cold-tolerance
genes thus may help in the development of crop plants that can
survive frigid temperatures. This optimism is supported by a recent
publication from Michael Thomashow's group at Michigan State
University which provides some valuable insights into how plants
respond to cold temperatures (1). The research shows for the first
time that freezing tolerance in plants can be enhanced through
insertion of a single gene involved in cold acclimation.

Thomashow's strategy has been to understand the process whereby
plants exposed to low, non-freezing temperatures somehow learn to
put up with subsequent freezing temperatures. For instance,
cold-acclimated rye plants can survive temperatures of up to -3=F8C.
The underlying reasons for this phenomenon appear to be complex,
but it is known that cold acclimation is controlled by many genes
and that cell membranes are particularly vulnerable to cold damage.
Thomashow and colleagues have isolated many genes that are turned
on during cold acclimation in Arabidopsis. One such gene is COR15a,
which is speculated to have a role in freezing tolerance.=20

The Michigan State group developed transgenic Arabidopsis plants
expressing the COR15a gene in a constitutive manner.  In normal
plants this gene is turned on only through cold acclimation, while
the transgenic plants showed COR15a gene product in both cold
acclimated and non-acclimated plants. Chloroplasts in leaves of
transgenic plants showed reduced damage to freezing temperatures
compared to those from the control plants. Further, in
collaboration with Peter Steponkus and colleagues at Cornell
University, it was found that protoplasts isolated from transgenic
plants survived better at sub-zero temperatures (18% better
survival at -6.5=F8C) than the controls.=20

Although the COR15a gene produces a chloroplast-targeted protein,
the results indicate that the expression of the gene may also
affect other cellular functions including improving the
cryostability of the plasma membrane. The COR15a gene enhanced the
freezing tolerance of chloroplasts in engineered plants by almost
2=F8C which was nearly one-third of the increase seen due to
cold-acclimation. While this might not appear to be a large
increase, a 2=F8C improvement in freeze tolerance could potentially
benefit certain crop plants.=20

According to Thomashow, there are many more COR genes known to
scientists. If introduced together into a plant, even more dramatic
cold tolerance, especially at the whole plant level, may be
achieved. Ongoing research in the Michigan State lab is striving to
understand more about the intricacies of plant gene expression in
response to freezing temperatures. This knowledge may empower
scientists to develop crop plants which can brave the cold.=20

(1)  Artus, N. N. et al. 1996. Proc. Natl. Acad. Sci. 93:

C. S. Prakash
Center for Plant Biotechnology Research
Tuskegee University=20


The World Health Organization (WHO) and the United Nations
Children's Fund (UNICEF) have published their joint "State of the
World's Vaccines and Immunization" report
/WHOProgrammes.html). This report chronicles the progress of the
Expanded Program on Immunization (EPI) to vaccinate the world's
children against polio, measles, neonatal tetanus, diphtheria,
pertussis (whooping cough), tuberculosis, hepatitis B and yellow
fever. The UNICEF-discounted price for the original six EPI
vaccines is approximately  $15, of which $1 is for the cost of the
vaccines and $14 goes for program costs such as laboratories, cold
transport, personnel and research. In contrast, the world's first
genetically engineered vaccine against hepatitis B costs  $150 for
three doses. Many other vaccines including those against
Haemophilus influenza, rubella, chickenpox, cholera and typhoid
fever are not widely used in developing countries partly because of
their initial high costs. New vaccines under development, such as
those against pneumococcal disease, meningococcal meningitis,
shigella, enterotoxigenic E. coli, HIV/AIDS, and malaria are also
expected to have high initial costs and therefore to not be widely
available in developing countries.

To achieve the ambitious goal of expanding the number of vaccines
used globally, simpler and more economical methods of delivering
them are needed. Edible plant vaccines hold promise as ideal
candidates. Production of vaccines in plants would eliminate the
expenses associated with maintaining the cold chain, purchasing
needles and syringes, and training personnel. Additionally, it
would eliminate the risk of contamination by animal pathogens.
Researchers at the Boyce Thompson Institute for Plant Research have
successfully expressed the E. coli heat-labile enterotoxin
B-subunit in potato tubers and the Norwalk virus capsid protein in
tobacco and potato.  Enterotoxigenic E. coli causes acute diarrhea
and Norwalk virus causes acute gastroenteritis in humans. Feeding
of raw potato tubers expressing these proteins to mice resulted in
the production of specific serum and gut mucosal antibodies. These
studies demonstrate the feasibility of using transgenic plants as
a safe vaccine production and delivery system.

One important point to consider with this approach is that the
plant must be eaten raw in order to be effective, since cooking
would destroy the antigen. Potatoes, which are not generally eaten
raw, thus serve only as a model transgenic system. Bananas have
been proposed as a more real-world delivery system, since bananas
are more palatable to children and are a staple of many diets.
Another group at Thomas Jefferson University is similarly exploring
the use of transgenic tomatoes as a delivery system for rabies
vaccines. Clearly the next step in the development of this
technology is to demonstrate in the vaccinated animal the induction
of a protective immunological response upon challenge with the
appropriate pathogen.  If this proves successful, then the efficacy
of the procedure should be ready for testing in human preclinical

(1)McGarvey, P.B., J. Hammond, M.M. Dienelt, D.C. Hooper, Z.F. Fu, B.
   Dietzschold, H. Koprowski,  and F.H. Michaels. 1995. Bio/Technology
(2)Mason, H.S., J.M. Ball, J.J. Shi, X. Jiang, M.K. Estes, and C.J.
   Arntzen. 1996. Proc. Natl. Acad. Sci. USA 93:5335-5340.

Eric A. Wong
Department of Animal and Poultry Sciences
Virginia Tech=20



The Entomology meeting included a half-day symposium on genetically
engineered arthropods. As one of the organizers, David O'Brochta
(University of Maryland Institute for Biotechnology), opened the
session with an overview of where the field is now by noting that
entomologists can now produce transgenic arthropods but only to a
limited extent. There have been a number of strategies employed to
achieve DNA mediated changes in insect phenotypes so far. Full
development of the technology, however, awaits better solutions to
three related problems: DNA delivery, DNA recombination, and
transgenic recognition.=20

Delivery and recombination systems need to get DNA stably
integrated into germ cells. Transgenic arthropods have been
reported following the direct injection of DNA into the haemocoel
of a reproductive female using transposable element-based
integration vectors. Microinjection of eggs has had some success,
but is not practical where the egg is very small or has a hard
shell, or where the insect bears live young. Newer techniques make
use of Sindbis virus vectors, or change insect phenotype through
the genetic alteration of an insect symbiont. There are additional
strategies being developed such as the use of modified retroviruses
that are likely to be successful as well. Recognition of
transformed individuals relies on the presence of screenable
markers. Here the options are expected to increase beyond the
currently available traits such as eye color or expression of green
fluorescent protein.

The most important point to be made is that limited solutions to
all of the problems associated with making transgenic arthropods
have been found. Although a transformation system is not yet
available, i.e. an efficient, robust, reproducible and relatively
simple method, it is clear that this is now just a matter of time.

David Andow (University of Minnesota) observed that given the
imminent arrival of transformation systems, it is prudent to begin
considering how the risks of transgenic insects and their release
into the environment might be assessed. Understanding how risk will
be assessed, particularly by regulatory agencies, can serve to
guide researchers in the early stages of designing field test
experiments. A number of models of risk assessment were discussed
and the underlying assumptions of each model were articulated.
Perhaps the most workable model considers the specifics of each
organism and each release on a case-by-case basis, allowing
specific questions to be addressed.

The regulatory view was presented in a talk prepared by Orrey Young
(USDA/APHIS Transgenic Arthropod Team) and given by Ralph Stoakes
(USDA/APHIS/PPQ Western Region). Although transgenic arthropod
technology is still in the early phases of development APHIS has
been proactive in addressing the issue of release by establishing
a team of scientists who are ready to review applications for
permits to take transgenic arthropods out of the laboratory.=20

While the rules and regulations under which permits will be
evaluated is mandated by law, the mechanism scientists must employ
to complete and submit permit applications is determined by APHIS.
The arthropod team has taken a relatively new approach to this
process by employing the internet. All applications for the release
of transgenic arthropods are posted on the internet and are
available for public and scientific scrutiny
/arthropod/). Comments and evaluations, solicited and unsolicited,
are also posted. One goal of the arthropod team is to promote an
interactive relationship with the scientists developing and using
this technology and at the same time provide those with a concern
for this technology an opportunity to be part of the review

Gerald Franz (FAO/IAEA, Siebersdorf, Austria) discussed a classic
system of genetic control, the Sterile Insect Technique (SIT). This
methodology uses ionizing radiation to sterilize insects which are
then released to breed with natural populations. SIT is currently
being used to control Medfly in Guatemala, Argentina and the Los
Angeles region; up to one billion sterile Medflies are released
worldwide per week. Other insects, such as tsetse fly on the island
of Zanzibar and the New World Screwworm in Mexico, are also being
controlled effectively using this method.=20

Medfly SIT could be improved with certain genetic improvements in
the released flies.
One simple improvement would be the incorporation of a gene that
would permit the unambiguous identification of release individuals
from wild individuals. Another improvement would be the
incorporation of a gene or genes that would permit the elimination
of females from mass-reared populations. Transgenic Medflies have
been created using a transposable element called Minos and the
transposable element Hermes looks equally promising. We can now
seriously consider the development of Medfly strains that have the
genotypes and phenotypes desired.

Frank Collins (Centers for Disease Control and Prevention)
described initiatives to genetically control disease transmission
by altering mosquitos so that they can no longer act as malaria
vectors. Conversion of a mosquito (Aedes aegypti) from being vector
competent to being vector incompetent by expressing a transgene has
been demonstrated recently by Olson et al. These investigators used
a Sindbis virus based expression system to transiently express an
antisense RNA that interfered with Dengue virus replication.
Although not permanently transformed, insects with the antisense
RNA were no longer capable of transmitting Dengue. The Hermes
transposable element was shown to have some potential to function
in mosquitos but it has not been used to create a transgenic insect
as yet. Permanent germline transformation is still not possible.=20

Frank Richards (Yale University), who also is interested in
converting disease vectors, rather than eradicating them, described
a unique strategy for achieving this goal. His group works with a
blood-sucking fly (Rhodnius prolixus) which harbors a bacterial
symbiont in its gut and which vectors trypanosomes (Trypanosoma
cruzi), parasitic flagellates that cause Chagas' disease. The
bacterial symbiont has been successfully engineered to express
cercropin A, a natural insect defense protein that makes pores in
membranes. When flies are cured of the naturally occurring symbiont
and their gut repopulated with the genetically engineered strain,
the insects lose their ability to harbor trypanosomes. Richards
described the development of a formulation of these genetically
altered symbionts, called CRUZIGUARD, which can be applied to the
walls of houses. The product is nearing the field trial stage.=20

In his closing remarks, David O'Brochta emphasized that the routine
use of insect biotechnology is not far off. Much of the effort in
the immediate future will be to determine which of the various
transformation or modification systems being developed will be most
appropriate for particular insects and applications. The problem of
identifying transgenic insects is still a pressing problem that
will receive considerable attention in the short term. In the
longer term the technology will be used in ways that are analogous
to its uses in plant and animal breeding. This will involve the
genetic improvement of honeybees and silkworms, disease resistance
and product improving modifications. Finally, transgenic insects
will be used for gene farming in which they serve as bioreactors
for producing products of commercial interest. Insects may have
advantages over using large mammals or plants under some

Pat Traynor
Information Systems for Biotechnology

David O'Brochta
Center for Agricultural Biotechnology
University of Maryland=20



Industry is  still waiting a decade after the Environmental
Protection Agency (EPA) declared it would clarify the regulation
of transgenic plant-pesticides under the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA)(1). The underlying problem
is that genetically engineered plant-pesticides do not fit the
paradigm for regulating conventional pesticides. In the absence
of a new rule, EPA has been applying existing and proposed (2)
regulations to the novel products moving through the registration
process. Exacerbating the situation is poor communication between
the registration and enforcement units within EPA and a shifting
interpretation of FIFRA.

One example of the resultant problems is the citation of Northrup
King (NK, now called Novartis Seeds) for violations of FIFRA with
regard to handling of transgenic corn under an EPA experimental
use permit (EUP). An EUP allows limited pesticide production for
the purpose of data collection during the product development
phase. The specific violations were for selling and distributing
(EPA lingo for importing) an unregistered plant-pesticide;
failure to file a Notice of Arrival; and failure to register
production facilities. Since provisions in FIFRA allow fines to
be assessed on a per shipment basis, the resultant fine levied
against NK was relatively substantial. While the EPA press
release (3) suggested that EPA's purpose in taking enforcement
action against NK was to ensure "that pesticides produced under
new technologies do not pose any environmental or health risks,"
the violations, according to Dea Zimmerman, EPA Region 5, were
purely technical, resulting from missing paperwork.=20

Some of the events surrounding the violations clearly were unique
to NK; it appears that no other companies have had similar
problems. In anticipation that registration of their Bt corn
product would be accomplished by March 1996, NK prepared for
entry into the marketplace by producing large amounts of hybrid
seed in Chile. Registration was delayed, however, and the
shipments arrived without a Notice of Arrival in violation of
FIFRA. EPA invented a process specifically for transgenic plant-
pesticides, called Plant Propagation Registration, which allows
companies to increase seed production in anticipation of
registration. Presumably, the violation charged to NK would not
have occurred if the company had followed this procedure.=20

In August, 1996, NK received registration of its new product,
i.e., the insecticidal protein and the genetic material needed to
produce it. The pesticide label, which normally appears on a
pesticide container, will remain in the registration file rather
than be printed on seed bags. Instead, NK is required as a
condition of registration to attach to the bags of hybrid seed a
tag which states:

=07    the seed is protected against European corn borer by a
     registered pesticide;=20
=07    a grower's guide is available;=20
=07    the seed may not be sold or used in certain areas where Bt
     cotton is grown (a precaution for pest resistance

The tag will also state that glufosinate ammonium is not
registered nor recommended for use on the corn even though the
transgenic seed produces a protein which increases its tolerance
to the herbicide. With the registration now in place, NK can move
hybrid seed without the restrictions which led to the violations.

Under the present interpretation of FIFRA, facilities where the
initial plant transformation is performed and where seeds of the
transgenic inbred line are processed are considered by EPA to be
pesticide production facilities and must be registered as such.
EPA considers the inbred corn as the means to transfer the active
ingredient (defined as the insecticidal protein and the genetic
material required to produce it) to the end product, hybrid seed.
However, EPA will not require registration of those facilities
where transgenic hybrid seed is produced from inbred lines. The
transgenic hybrid seed itself is considered to be a "treated
article", and therefore is exempt from FIFRA, analogous to
treated fenceposts. This exemption spares growers of Bt-corn from
being regulated as pesticide producers and puts the primary
weight of regulatory compliance on the registrant.=20

According to Phil Hutton, an EPA Product Manager, it has been
easier for developers of transgenic plant-pesticides to
understand the regulations if they have experience dealing with
traditional pesticides. EPA is preparing a workshop on oversight
of transgenic plant-pesticides for the seed industry. The
eventual publication of the new rule, which has again been
delayed several months, will provide much needed guidance to

(1) 1986. The coordinated framework for regulation of
    biotechnology.  Federal Register 51:23302-23393.
(2) 1994. Plant-pesticides subject to the Federal Insecticide,
    Fungicide, and Rodenticide Act and the Federal Food, Drug, and
    Cosmetic Act; Proposed policy; Notice. Federal Register 59:60495-
(3) EPA Region 5 Press Release. Nov. 4, 1996. EPA nets $162,500
    for pesticide violations; first action of its kind under
    pesticide law. No.96-OPA255.

Jan Klein


Starting April 15, 1997, users of certain infectious or toxic
agents will need to comply with new reporting requirements. In
response to the threat to human health and safety from the
illegitimate use of infectious agents, the Department of Health and
Social Services (HSS), Centers for Disease Control and Prevention
(CDC), developed a rule entitled "Additional requirements for
facilities transferring or receiving select agents". The
Antiterrorism and Effective Death Penalty Act of 1996 established
new provisions to regulate the transfer of hazardous agents and
required HHS to issue rules to implement these provisions. =20

According to the statement accompanying its publication, the rule
was designed to:
=07  establish a system of safeguards to be followed when specific
   agents are transported;
=07  collect and provide information concerning the location where
   certain potentially hazardous agents are transferred;
=07  track the acquisition and transfer of these specific agents;
=07  establish a process for alerting appropriate authorities if an
   unauthorized attempt is made to acquire these agents.

The core of the new rule, Appendix A, lists the select agents which
are subject to the reporting requirement: 13 viruses, 7 bacteria,
3 rickettsiae, 1 fungus, and twelve toxins.  Included in the list
of toxins are aflatoxins, botulinum toxins, and ricin. Also subject
to the rule are genetic elements from the select agents that
contain a nucleic acid sequence(s) which, if inserted into an
appropriate host system, are reasonably believed capable of
producing disease or toxicosis. Appendix A also specifies
exemptions to the rule.=20

Commercial suppliers of these select agents, as well as government
agencies, universities, research institutions, individuals, and
private companies that transfer or obtain these agents must
register with HSS or with an organization authorized by HSS.
Certified clinical laboratories that utilize these agents for
diagnostic, reference, verification, or proficiency testing
purposes are exempt from this rule. The rule allows assessment of
a fee to cover the costs of the registration service. The fee
structure has not yet been established, but registration could cost
more than $1000, especially if a facility inspection is done. An
anticipated result of the new rule is that many facilities will
remove from inventory those select agents for which there is no
current use.

The final rule was published in the Federal Register, October 24,
1996 (Vol.61 no.207).  To request a registration packet, fax your
name and address to the Office of Health and Safety at (404)639-
3236. For additional information, contact Dr. Jonathan Y. Richmond,
Director, Office of Health and Safety, Centers for Disease Control
and Prevention, 1600 Clifton Road, Mailstop FO5, Atlanta, GA 30333;



Each year, the accounting and consulting firm Ernst & Young (E&Y)
publishes a status report on the biotechnology industry. In the
1997 report entitled "Biotech 97 - Alignment"  the authors question
the future of agricultural biotechnology as a sector within the US
biotech industry (1).

The section of the report dedicated to agbiotech begins, "For the
agbiotech sector, the handwriting may be on the wall." This
prediction is driven by several facts. First is the consolidation
that has taken place within the agbiotech sector, including
DowElanco's investment in Mycogen and Monsanto's equity stakes in
DeKalb Genetics, Agracetus, and Calgene. E&Y notes that Calgene was
the agbiotech industry's flagship company, and now an agrochemical
giant, Monsanto, is the key agbiotech company.=20

E&Y also refers to lower returns on investment in the agbiotech
sector versus biopharmaceuticals as another obstacle to growth.
They argue that consumers are willing to pay more for novel
biotherapies than for novel seeds, despite the high cost of
development that agbiotech companies also face. Lower returns on
investment make it more difficult for agbiotech firms to entice
venture capital and public equity investors. With relatively few
agbiotech start-ups in the wings, E&Y states, "many people are
wondering if the US agbiotech game is better played by large
chemical and agricultural companies with deep pockets" (1).

The report goes on to say that the overall biotech industry in the
US is getting more concentrated in the health care and supplier
sectors, although this is not the case in Europe where there is a
much more even distribution of companies across areas including
therapeutics, industrial supply, agbiotech, and others. The
agbiotech sector also makes up a much larger percentage of the
biotech industry in Canada, as well. Results from a separate survey
recently undertaken by E&Y's Toronto office show strong growth in
the Canadian agrifood sector, while the percentage of firms in the
health care sector has decreased to 55% down from about 67% two
years ago. This is in contrast to the health care sector in the
United States, that accounts for 87 percent of the biotech industry

(1) K.B. Lee and G.S. Burrill.  1996. Biotech 97: Alignment, The
Eleventh Industry Annual Report.  Ernst & Young, Palo Alto, CA.
(2)  S. Yanchinski.  1996. Number of Canadian Biotech Firms Doubles
in Last Two Years, to 250.  Genetic Engineering News,  16(21):44.

William O. Bullock
Institute for Biotechnology Information, LLC
Research Triangle Park, NC


Editor's Note: The following article was developed from a paper
entitled "Impact of transgenic viral resistance on seed potato
certification" written by T.L. German and S.A. Slack and published
in The Badger Common'Tater 11:41-54 (1996).

The products of agricultural biotechnology are said to accelerate
existing trends in the agricultural marketplace. The best known
example of this phenomenon is Monsanto's recombinant bovine
somatotropin which was accused of bankrupting small dairy farms
even before the product was  approved for commercial distribution.
Thomas German and Steven Slack (University of Wisconsin-Madison)
suggest that entry into the marketplace of transgenic virus
resistant (VR) potatoes may also accelerate existing trends in
potato production. NatureMark, a subsidiary of Monsanto, plans to
have two types of virus resistant potatoes approved for
commercialization in 1998, with seed available in limited
quantities in 1999. NewLeaf Plus is a Russet Burbank variety with
resistance to potato leaf roll virus (PLRV) and to Colorado potato
beetle; NewLeaf Y will have resistance to potato virus Y (PVY) in
addition to beetle protection and will be available in three
varieties, Russet Burbank, Russet Norkotah, and Shepody.

German and Slack believe that the introduction of VR potatoes will
accelerate the trend within potato production toward fewer and
larger farms. They further point out that since a large investment
of capital, time and market development is required to bring
transgenic plants into the marketplace, their introduction is
likely to take place on a large scale primarily, but not
exclusively, in the private sector. The authors also suggest that
the new varieties may contribute to the current trend towards
vertical integration as potato producers enter into direct or
exclusive contracts with cultivar owners. The authors envision a
production scheme in which "the producers of transgenic cultivars
will generate seed for distribution to contract seed growers who
have contracts with commercial producers that in turn will have
contracts with processors or other end users (who may or may not be
owned by the same corporations)."

Aggressive marketing will help recoup the investment, but will
likely have the side effect of reducing the use of some less
strongly supported public and minor use varieties, thereby=20
increasing homogenization of the system. Varietal patents and
variety protection are also being used increasingly to help defray
costs of development for traditionally derived cultivars as well as
for transgenics.

The rate and level of adoption of transgenic VR lines will affect
their overall impact on the potato industry. An immediate benefit
to growers will be the lowering of virus reservoirs within a field.
Additionally, VR plants will, in effect, be more tolerant to the
presence of aphids which are the natural insect vectors of PLRV and
PVY. As a result, less pesticide will need to be applied. On the
other side of the equation, though, a build up of aphid populations
in potato fields will likely be a concern for adjacent non-
transgenic crops. According to Jennifer Feldman of NatureMark, use
of the transgenic varieties by growers will be carefully controlled
in order to manage the potential for development of resistance; it
would be counterproductive to flood the market.=20

The transgenic VR potato varieties fit well within the current
system of seed certification which was developed early in the
century. Seed certification insures potato seed quality by setting
standards for varietal purity and tolerances for viruses and other
diseases. A recent trend has been to reduce the number of
generations prior to release of seed to the commercial grower,
resulting generally in increased vigor and less yield loss due to
disease. The current standard inspection process within seed
certification programs is expected to provide monitoring of VR
potatoes to eliminate off types and detect any breakdown of
resistance. In summary, German and Slack conclude that the "most
significant changes anticipated from this new technology will
likely occur as a result of continued homogenization and
specialization within the industry."

Jan Klein

*  *  *  *  *  *  *  *  *  *  *  END   *  *  *  *  *  *  *  *  *  *  *=20

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. P.L. Traynor, Editor.

Information Systems for Biotechnology, 120 Engel Hall, Virginia Polytechnic
Institute and State University, Blacksburg, VA 24061-0308, tel:=
fax: 540-231-2614, email:

For internet access to the News Report, textfiles, and databases use one
of the following procedures. =20

1. Through WWW:

2.To have the News Report automatically emailed, send an email message to and type subscribe newsreport [your-name] in the
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3. Use ftp to connect to  Use "anonymous" as your user-id,
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