
In This Issue:
Realignment at APHIS Should Not Affect "Customer
Service"
Major International Biosafety Conference Draws Renowned Speakers
In Vivo Markers Could Help Mitigate Potential Risks of GMOs
Transgenic Grapes - One More Hurdle Overcome
New Super-Promoter Drives Very High Expression of Introduced Genes in Plants
Revved up Chitinase Expression Fights off Fungal Pathogens
Woolier Sheep
Recombinant Proteins from Milk of Transgenic Animals
Report on European Agricultural
Biotechnology
Plant Tissue Culture Information Exchange
When USDA's Animal and Plant Health Inspection Service (APHIS) reorganized in 1988, the new Biotechnology, Biologics and Environmental Protection (BBEP) unit was formed from other small components of the Agency. A biotechnology policy staff from the Administrator's office served as a nucleus. Joining the policy staff was a permits group and an environmental analysis unit from Plant Protection and Quarantine (PPQ), plus two units from Veterinary Services in charge of veterinary biologics licensing and inspection. During the next eight years, the BBEP staff grew substantially and multidisciplinary teams were built to license veterinary biologics and review environmental impacts of genetically engineered plants and microorganisms.
During the last decade, however, the world of agricultural biotechnology continued to evolve. The once young biotechnology industry matured, and trade issues rather than field testing became the key concern of regulators worldwide. Therefore, in an effort to remain viable and ready to meet new challenges, APHIS decided to realign its staff functions.
As of October 1, 1996, BBEP will cease to exist as a unit. The veterinary biologics program will be consolidated into Veterinary Services, some environmental functions will be aligned with the Agency's central policy support staff, and the biotechnology program and environmental testing and monitoring groups will be moved as a unit to the PPQ program.
According to John Payne, Acting Deputy Director of BBEP, the realignment will foster closer coordination between the biotechnology program and other units in the Agency responsible for phytosanitary standards and pest risk analysis. These changes will have no effect on USDA's biotechnology regulations, points of contact, or the processes followed for obtaining field testing permits or notifications, or petitions for non- regulated status. The strong ties that link USDA, the Environmental Protection Agency, and the Food and Drug Administration to ensure a coordinated regulatory framework will remain as strong as ever.
"The realignment will help put APHIS in an excellent position to meet future challenges, such as those related to international trade and the harmonization of regulations," said Payne. With the new emphasis on international trade comes a need for close coordination with others in the agency responsible for phytosanitary standards and those who conduct pest risk analysis in support of international trade in produce and commodities. APHIS may also explore new ways to include environmental analysis in the early stages of program planning and analysis.
The BBEP realignment is part of an overall cultural change taking place at APHIS, according to Payne. "The vision is to provide customers better service with programs that reflect their needs in an ever changing global economy."
Report compiled from USDA sources.
MAJOR INTERNATIONAL BIOSAFETY CONFERENCE DRAWS RENOWNED SPEAKERS
The 4th International Symposium on The Biosafety Results of Field Tests of Genetically
Modified Plants and Microorganisms will be held on July 14-17 at Tsukuba Dai-ichi Hotel,
Tsukuba, Ibaraki, Japan. This symposium is being organized by the Japanese International
Research Center for Agricultural Sciences with the cooperation of USDA, EPA and DG
XII/EC. The deadline for registration is June 20.
For the practical use of genetically modified plants and microorganisms, extensive field
testing has been carried out in a large number of countries. Procedures to secure the
protection of the environment and public health, termed "Biosafety", are vital components of
each of the field tests. This is the fourth meeting which brings together researchers from
various sectors, to discuss scientific issues on biosafety evaluation, field tests toward
commercialization and new international developments and harmonization.
Preliminary Agenda
Day 1 (July 14) - Registration and Reception
Day 2 (July 15) - Emerging Approaches
PANEL I: New Research Techniques and Diagnostic Tools for Biosafety Evaluations
Moderators: M. Keller (U of Bielfeld, Germany) and J. Kurisaki (National Institute of Animal
Industry, Japan)
S. Lehrer (Tulane University, USA) - Recent development in approach to allergenicity
C. Ramos (CSIC, Spain) - Assay on biodegradative abilities of biologically contained
microbes
Y. Shinmoto (NFRI, Japan) - Allergenicity forecast using immortalized cells
J. Schiemann (IBPV, Germany) - New methods and results in monitoring field release of
genetically modified organisms
S. Warwick (Agri-Food Canada) - Use of biosystematics and molecular phylogenies for
biosafety evaluations
PANEL II: Emerging Biosafety Field Testing Capacity / Capability in Developing Countries
Moderators: R. Casper (Braunschweig, Gernmany) and K. Minami (JIRCAS, Japan)
J. Cohen (ISNAR, Netherlands) - International activities on development and transfer of
biotechnology for developing countries
S. Jia (ABC, CAAS, China) - Current development of field tests and guidelines in China
M. Madkour (AGERI, Egypt) - Developments in agricultural biotechnology including white fly
resistance in the Middle East
S. Sutat (NCGEB, Thailand) - Current development of field tests including transgenic tomato
in Thailand
A Villalobos (CINVESTAV, Mexico) - Field tests on potatoes and vegetables in Mexico
M. Zimmermann (EMBRAPA, Brazil) - Current activities on field tests and safety issues in
South American countries
Day 3 (July 16) - Biosafety Results
PANEL III: Field Experience in Using Microorganisms as Bioindicators, Biosensors, or
Biomonitors
Moderator: M. Schechtman (BBEP/APHIS/USDA, USA)
D.Daubaras (U of I at Chicago, USA) - Developing genetically modified bacteria
(Pseudomonas) for bioremediation and degradation
M.P. Nuti (U of Padova, Italy) - Field release of genetically modified biofertilizers and
phytostimulates
K. Watanabe (Kyushu AES, Japan) - Detection and identification of microorganisms in soil
and natural environments
F. Dane (U of Auburn, USA) - Field detection of phytopathogenic bacteria by the use of
bioluminescence
PANEL IV: Agronomic and Food Products in the Marketplace - Lessons Learned
Moderators: R. Downey (Agri-Food Canada) and Z.L. Chen (U of Peking, China)
S. Chandler (Florigene Ltd., Australia) - International marketing of genetically modified
carnation
D. Re (Monsanto Co., USA) - Marketing Monsanto's genetically modified crop plants
P. Rudelsheim (Plant Genetic Systems, Belgium) - Marketing PGS's genetically modified
crop plants including rape seed
S. Van Wert (AgrEvo NOR-AM, USA) - Marketing AgrEvo's genetically modified crop plants
including herbicide tolerant maize and rape seed
PANEL V: Defining Unique Science Issues in Biosafety Risk Assessment
Moderators: J. Beringer (Bristol U, United Kingdom) and M.P. Nuti (U of Padova, Italy)
T. Stone (Monsanto Co., USA) - Developing insect resistance by the use of Bt toxin
A. Wood (Boyce Tompson Institute, USA) - Control of insects by the use of modified viruses
S. Lohrke (University College Cork, Ireland) - Experiences in molecular ecology of
rhizospheres with microbial releases
T. Sasaki (NIAR, Japan) - Progress in the rice genome project and its cross-species
implication
M. Tepfer (INRA, France) - Transgenic virus-resistant plants and new plant viruses
K. Shinozaki (JIRCAS,Japan) - Developing transgenic tolerance to stresses including
drought in plants
Day 4: (July 17) - Biosafety Results (continued)
PANEL VI: International Harmonization of Safety Issues
Moderators: T. Medley (APHIS/USDA, USA) and K. Hayashi (STAFF, Japan)
S. Barber (Agri-Food Canada) - Development and implementation of the Canadian approach
to regulation of plants with novel traits
Z.L. Chen (U of Peking, China) - Concept and related issues in development and safety
evaluation of genetically modified agricultural products in China
J. Gopo (SIRDC, Zimbabwe) - Activities and direction in development and safety evaluation
of genetically modified plants in African countries
H. Marquard (Dept of Environment, United Kingdom) - Current and future trends in
harmonization of safety issues in Europe and internationally
C. Vicien (Sec of Agriculture, Fisheries and Food, Argentina) - Current and future trends in
harmonization of safety issues in Central and South American countries
For questions concerning registration, contact Dr. Keiji Oga at +81-298-38-6342 (fax) or
oga@jircas.affrc.go.jp. The registration fee should be paid by a bank draft or money order for
30,000 Japanese yen made payable to "BIOSAFE4". The name of the registrant should be
indicated on the draft or money order. Bank transfers should be made to: JOYO Bank,
Kenkyu-gakuentoshi Branch; Account Name: BIOSAFE4; Account No: 1308537. All payment
must be Japanese yen. Hotel information will be sent to registrants.
IN VIVO MARKERS COULD HELP MITIGATE POTENTIAL RISKS OF GMOs
University and corporate researchers are genetically modifying viruses, microbes, plants,
and animals for various purposes. Until recently there has been no easy, cost-efficient
method to detect, in a mixed sample, which organisms are modified and which are not.
Having this information becomes important if one is concerned with tracking individuals or
transgenes in time and/or mitigating potential long-term ecological effects of the
environmental release of transgenic organisms. If an organism were engineered with an in
vivo marker that could be visually detected in real time, then it could be easily monitored.
The ramifications of the ability to easily monitor transgenic organisms are not trivial. The
existence of a monitoring system will allow researchers to study gene flow, persistence and
other ecological effects of transgenic organisms introduced into the environment.
The discovery of green fluorescent protein (GFP), and the cloning of the gene (1), have
allowed researchers to engineer organisms to fluoresce green under ultraviolet light (2).
GFP is the first universal in vivo marker that can be detected in real time, and requires no
substrate or expensive equipment for detection. However, only recently has GFP gene
expression been high enough to light up, say, whole plants (3). My laboratory has recovered
transgenic plants in which the entire plant glows green under an ultraviolet light
(View at http://www.uncg.edu/~cnstewar/license.htm).
An agricultural gene of interest may be fused
translationally or transcriptionally, or simply linked to GFP, allowing easy identification of
initially transformed individuals as well as detection of any hybrid progeny carrying the
transgene. Thus the ability to use GFP as an ecological marker in higher organisms makes
subsequent monitoring in the environment very simple.
There are several applications of such technology. Prasher (2) mentions the possibility of
using GFP to monitor sterile insects released into the environment, and to detect microbes
from fermentors that are not intended to be released. It also would be useful to keep track of
microbes that are used in bioremediation. A novel use for GFP as a biomonitor for
baculoviruses was recently published (4). In this report, GFP-engineered virus was used to
infect insects, and the insects were subsequently shown to fluoresce green.
The most widespread potential use of in vivo-marker linked tracking will be for monitoring
transgenic plants. Canola and sunflower, for example, have breeding systems that are
problematic because transgenes may be transferred into nearby weedy relatives. If the
transgenes are for traits that can confer higher fitness, such as resistance to herbicides,
disease, or insects, then it is possible for the recipient weed to gain a selective advantage
and become weedier. In the case of a plant like sunflower, which has its center of genetic
diversity in the U.S., introduction of transgenic cultivated sunflower with higher fitness could
possibly decrease the genetic diversity of wild sunflower, if the transgene were to be
transferred into the wild populations.
GFP technology could help in the mitigation of potential ecological effects of large-scale
transgenic plant production. For example, since we cannot fully predict how an escaped
transgenic insecticidal plant may affect natural ecosystems, it may be 20 years before the
consequences are clear. If plants containing transgenes can be easily tracked, negative
effects may be evident sooner. Biotechnology companies may find it beneficial to use in vivo
markers to limit their liability and demonstrate good stewardship. It is also likely that
regulatory agencies may require mitigation for the deregulation of certain organism-gene
combinations. Now that the technology is available, it would seem prudent to use it.
References
C. Neal Stewart
European cultivars of Vitis vinifera produce the biggest share of the world's wine and table
grapes, but have proven difficult to genetically engineer. Grapes produce high levels of
tannins and phenols, compounds that oxidize rapidly and interfere with cell culture and
transformation. North American Vitis species used in fruiting hybrids or rootstocks, in
contrast, are more amenable to cell culture and Agrobacterium transformation, and several
transgenic lines have been obtained. Now, in the May issue of Nature Biotechnology, a
group of scientists working for the Agricultural Research Organization, The Volcani Center
(Bet-Dagan, Israel) report a significant advance towards transformation of Vitis vinifera.
Embryogenic callus of grape plants cocultivated with Agrobacterium exhibits a browning
reaction and cell death 48 hours after the tissue is transferred to regeneration medium. The
response is independent of bacterial concentration, duration of cocultivation, and exposure
to antibiotics used to eliminate Agrobacterium. Necrogenesis is correlated, however, with an
increase in peroxidase activity observed 24-36 hours after the end of cocultivation.
To reduce browning, various antioxidants were added to the cocultivation medium.
Dithiothreitol (DTT) and polyvinylpolypyrrolidone (PVPP) were effective, but only to some
extent. Far better inhibition of browning was achieved by cocultivation in the presence of
PVPP followed by transfer to a double-layer medium containing PVPP in the solid layer and
DTT in the liquid layer. After seven days in the dark, embryogenic calli were transferred to
solid selection medium for 30 days prior to regeneration. Sixty-three percent of these calli
were able to regenerate transformed grape plants.
Parallel experiments with tobacco leaf-disks confirmed that use of the antioxidants during
cocultivation did not reduce the virulence of Agrobacterium; transformation efficiency was the
same with or without added antioxidants.
For grapes, the door has opened wider to improvements through biotech. Use of sprays to
control diseases caused by powdery and downy mildews could be reduced or eliminated by
engineering important cultivars with fungal disease-resistance genes. Popular table grape
varieties could become more attractive to consumers if they were engineered for
seedlessness. And, as the authors suggest, the procedure may be applicable to other plant
species, such as mango, in which a browning reaction is associated with Agrobacterium
inoculation.
Pat Traynor
NEW "SUPER-PROMOTER" DRIVES VERY HIGH EXPRESSION OF INTRODUCED
GENES IN PLANTS
Transgenic plants have now become a commercial reality and genetic transformation is
routinely done in most crop species. However, achieving a high expression of the introduced
foreign gene in plant cells is still a challenging task. Especially in those projects aiming to
develop plants as "biofactories" to produce novel enzymes, pharmaceuticals and industrial
compounds, it is critical that introduced genes churn out the corresponding proteins in large
amounts to make the venture economically feasible.
The level of gene expression is, in part, a function of the promoter to which the coding region
of the gene is fused. Use of the most popular promoter in plant molecular biology research,
the 35S promoter from cauliflower mosaic virus (CaMV), usually results in production of the
foreign gene product at rates of less than one percent of the total protein. Improvements to
the CaMV 35S promoter such as the duplication of certain sequences and the addition of
enhancers have boosted expression, but for some applications, the levels need to be still
higher.
Now, a novel promoter developed at the laboratory of Stan Gelvin at Purdue University may
come to the aid of plant scientists frustrated by low expression levels of introduced genes. In
a "head-to-head" test, the new super-promoter resulted in 156-fold more GUS activity than
did the -800 CaMV 35S promoter of pBI121. Although actual protein levels were not
measured and other versions of the 35S promoter are somewhat stronger than the one used
in the test, the results are nonetheless quite impressive.
This promoter is derived from the soil-borne plant pathogen Agrobacterium tumefaciens
which causes crown gall disease and serves as a common vector to introduce genes into
plant cells. Gelvin and associates experimented with various combinations of regulatory
sequences from two genes from this bacteria: octopine synthase (ocs) and mannopine
synthase (mas). Among the many combinations they tested, a hybrid promoter combining a
triple repeat of the ocs activator sequence along with mas activator elements fused to the
mas promoter did the trick! Termed "(Aocs)3AmasPmas", the promoter is also referred to as
construction #5 in the publication where it is described in detail (1).
In transformed tobacco cells, expression of the GUS marker gene driven by this promoter
allowed detection of ten-fold more transformants than when the CaMV 35S promoter was
used. It is not likely that the new promoter affects transformation efficiency, but the elevated
level of marker expression made it easier to identify a higher proportion of transformed cells.
Expression levels were high in leaf, stem and root and in most cell types. The promoter was
also very active in cassava and cowpea, two crop plants which have appeared difficult to
transform using Agrobacterium.
In a paper soon to be published in the May issue of Plant Cell, Gelvin's group describes their
success in the use of this promoter to study very early transcription of introduced genes
(within 18 hours) in tobacco and maize. The CaMV 35S promoter was too weak to show any
activity at this time. Other researchers at various laboratories are now testing the new
promoter to see if it would help boost levels of expression of their introduced genes in plants.
The "Super-Promoter" has been licensed by Purdue University to Biotechnology Research
and Development Corporation (BRDC) of Peoria, Illinois. Those interested in obtaining the
promoter can contact Grant Brewen at BRDC (tel: 1-309-688-1188; fax: 1-309-688-1292).
Technical questions should be addressed to Stan Gelvin at 317-494-4939;
gelvin@bilbo.bio.purdue.edu.
Reference
C. S. Prakash
REVVED UP CHITINASE EXPRESSION FIGHTS OFF FUNGAL PATHOGENS
Constitutive over-expression of a chitinase transgene has been shown to confer increased
resistance to fungal attack in the field. A group of French and Swiss collaborators reported in
Nature Biotechnology (May, 1996) that transgenic oilseed rape (Brassica napus) plants
expressing a tomato chitinase gene exhibited an increased resistance to infection by three
pathogens, Cylindrosporium concentricum, Phoma lingam, and Sclerotinia sclerotiorum.
Trials were conducted at two locations under different climatic conditions.
Chitinases catalyze the hydrolysis of chitin, a polymeric component of fungal cell walls. The
potential use of chitinase for enhanced disease resistance gained momentum when work in
several labs demonstrated that transgenic plants expressing chitinase genes under the
control of the CaMV 35S promoter showed increased resistance in greenhouse trials.
The plants used in the field trial were third generation progeny of initial transformants, and
carried a single copy of the transgene. Different degrees of protection against the three
pathogens were observed, with a reduction of symptoms ranging from 23% to 79%. The
differences could be due to the biochemical composition and structure of the fungal cell
walls, localization of the recombinant chitinase, and type of interaction between the plant and
the pathogen.
Accumulation in the cell of proteins active against disease-causing organisms is one of the
many natural defense mechanisms plants use to resist pathogen attack. In some cases,
where this mechanism is too weak or appears too late to fully protect the plant, engineering
constitutive expression of a defense protein can boost tolerance to fungal pathogens.
Pat Traynor
Improvement of production traits through genetic manipulation has been a goal of
researchers generating transgenic livestock. However, successes to date have been limited.
In the February issue of Bio/Technology researchers from Lincoln University in New Zealand
report on the improvement of wool production in transgenic sheep expressing insulin-like
growth factor-1 (IGF-1).
IGF-1 is a 70 amino acid peptide that mediates many of the mitogenic actions of growth
hormone. To target IGF-1 expression to wool follicles, a mouse ultra-high-sulfur keratin
gene promoter was linked to an ovine IGF-1 cDNA. Five of 103 lambs born were transgenic
following the microinjection and transfer of 591 embryos. One ram, which showed expression
of the IGF-1 transgene in the skin, was mated with non-transgenic ewes. Transgenic
progeny sheared at 14 months of age showed a 6.2% greater clean fleece weight than
non-transgenic half-sibs.
Rate of wool growth and wool bulk, which is a measure of the ratio of wool volume to weight,
was significantly elevated in transgenic compared to non-transgenic animals. Wool
properties such as fiber diameter or medullation, which is a measure of the extent that the
fiber is filled with cells, was the same for transgenic and non-transgenic animals. For an
unknown reason, fiber strength was lower in transgenic males compared with transgenic
females or the average of non-transgenic animals. A significant finding of this transgenic
sheep project is the successful modification of a production trait in transgenic livestock
without any adverse effects on health or reproduction.
Using an alternative strategy, Australian researchers have produced transgenic sheep that
overexpress a sheep keratin intermediate filament (IF) type II gene. This gene is a major
protein of the central cortex of a wool fiber. Changes in fleece characteristics have been
documented for one transgenic ram and his progeny. Wool growth is thought to be limited by
the availability of the amino acid cysteine, which plays an essential role in the cross-linking
of keratin proteins. One approach that is being actively pursued to overcome this limitation is
the production of transgenic sheep containing the bacterial genes for cysteine biosynthesis.
Expression of these bacterial genes in the rumen, where the enzyme substrates serine and
hydrogen sulfide are present, would be expected to result in an increase in the concentration
of available cysteine for wool growth. Interestingly, the increased rate of wool growth
observed in the IGF-1 transgenic sheep indicates that dietary cysteine was not rate limiting
in that study. Transgenic sheep with enhanced wool growth or modified fiber properties are
now at hand. Perhaps in the future the classic children's nursery rhyme will need to be
updated to read "yes sir, yes sir, more than three bags full".
Eric A. Wong
RECOMBINANT PROTEINS FROM MILK OF TRANSGENIC ANIMALS
It has been demonstrated repeatedly that therapeutic proteins can be produced via
recombinant DNA technology, using microbes or large-scale animal cell cultures as
bioreactors. Prokaryotic microbial systems are desirable due to cost efficiency, but
inherently limited because they typically are unable to carry out post-translational
modifications such as glycosylation or folding; it is not uncommon that microbial recombinant
proteins are not biologically active. Many of these disadvantages are overcome in large-scale eukaryotic cell culture systems, but potential microbial contamination problems,
requirements for complex and costly media, and lengthy incubation times needed to build up
cell mass and generate the desired product, often make these systems unsuitable as an
alternative. Furthermore, downstream processing can be expensive and time-consuming for
products of microbial or cell culture systems.
Transgenic animals are likely to be a better solution since the intact organism is, in effect, a
collection of biosynthetic cells in high numbers and at optimum metabolism. Early work on
animal transgenesis was directed mainly at improving the production characteristics of farm
animals, but the unlikelihood of significant profit caused many to turn their attention to the in
vivo manufacture of pharmaceuticals and related products. Biological fluids, including blood
(and the hemolymph of insects), milk, egg white, and others, are all targets of intense
research and development efforts since they are likely to be the best sources of recombinant
proteins.
Blood is readily available in quantity, and has been an important source of useful proteins for
many years. Indeed, hyperimmune serum from large animals (such as horses) is still the
treatment of choice in some diseases of domestic animals. Other proteins are also obtained
from blood, serum, and/or plasma, but a limiting factor is the complex composition of these
materials, and the fact that high- or even low-level expression of some proteins and other
substances in the blood may profoundly affect the health of the producing animals.
Production of proteins in chicken eggs is becoming more common, and although the supply
from this source is potentially abundant, this aspect of transgenesis lags behind others.
Expression of recombinant proteins in insect hemolymph also has desirable facets, but the
supply per unit can be relatively low.
Milk is also readily collected and widely available. It has few degradative enzymes to alter
the integrity of recombinant products and its relatively simple constitution facilitates
downstream processing. Thus, expression of recombinant proteins in milk has become an
important strategy. Where and when the gene product will be expressed is controlled by the
promoter elements, a particularly important component in the whole process, since the
optimum situation is to limit expression to the mammary gland during lactation. The general
approach -- the transfer to an animal of a DNA construct having the regulatory sequences
from a milk protein gene and the structural sequences for the protein of interest -- has been
tested in many animals, including mice, rabbits, ruminants, and pigs, and shown to be
conceptually feasible.
Expression of transgenes in the mammary gland has been employed primarily to recover the
desired protein from milk, although expression of genes intended to alter the composition of
milk is also under development. It is also possible to change the composition of milk in
diverse ways. Many foreign proteins have been expressed, and this technology is now being
extended to modifiy milk composition by altering metabolic enzymes, fat, and other milk
components. A specific example is the addition of lysozyme or modified bovine K-casein to
cows' milk to facilitate different manufacturing applications.
A gene encoding a human glucosyltransferase, which generates the H-blood group antigen,
fused to the mouse whey acidic protein promoter, commonly used for expression of foreign
proteins from the mammary gland, was introducted into animals. Milk from these transgenic
animals contained not only the transferase itself, but modified glycoproteins containing the
H-antigen, as well. Thus, transgenic expression of the transferase in a heterologous species
can be accompanied by expression of secondary gene products. It may be that the structure
of milk oligosaccharides in one species can be changed by expression of the gene for an
appropriate enzyme from another.
Indeed, reports of success are increasing dramatically in number. Progress in recombinant
DNA technology and embryo manipulation and transfer has made introduction of genes
almost routine. While none has yet reached the market, several proteins have been
prepared on a large scale. Mice are routinely used to evaluate the gene constructs to be
transferred into larger animals, and can also be utilized to prepare recombinant proteins in
amounts as high as a few hundred milligrams. Rabbits and larger animals (sheep, goats, and
pigs) are also commonly used, and it is likely that some recombinant proteins aimed at
prophylaxis or therapy will soon be beyond the stage of early clinical trials. The slow but
definite progress toward improving efficiency gives reason for enthusiasm, and many
laboratories and individual investigators are applying these techniques. It has been
predicted that, by the turn of the century, about 10% of recombinant proteins will be prepared
from the milk of transgenic animals, and that this industry will be worth more than $100
million in the annual market.
J. Glenn Songer
European commercial agricultural biotechnology is thought by many to be at a competitive
disadvantage to the United States based on regulatory and other factors. A recent study
conducted by the consulting firm BioBridge of the United Kingdom (UK) entitled "European
Crop Biotechnology, Volumes 1&2" does not necessarily dispel that notion, although it does
describe a very productive and viable European industry (1,2).
Table I shows a list of EU field release and product development projects by crop,
demonstrating the diversity and extent to which transgenic crop commercialization has
evolved in Europe. The BioBridge study identified 1,900 projects in key European Union
(EU) countries that have direct relevance to the future of transgenic crops. Projects being
undertaken in the UK, Germany, and France account for 60 percent of these projects.
Although it is perceived that U.S. firms have a competitive advantage in the business of
ag-biotechnology, many of the leading companies investing in the technology are European,
including Ciba and Sandoz (merging to become Novartis), Rhone- Poulenc, Bayer, and
Zeneca. One of the reasons may lie in the fact that the overall European market for seeds is
likely larger than that in the U.S. BioBridge estimated the overall expenditures by commercial
organizations on crop biotechnology in the EU to be around Ecu 50-60 million per year (US
$61-74 million as of 5/31/96).
Transgenic crops have already reached the market in Europe. Zeneca genetically
engineered tomatoes which are being used to produce tomato paste which is now on the
market in the UK. The report indicates that these larger companies are the most likely to
develop crop biotechnologies, either on their own or through acquisition of smaller crop
biotech firms.
It is also noted that there seems to be some incongruity between the level of effort for
specific crops and the actual profitability of the markets. Although maize, sugar beet and
sunflower appear to be the most profitable markets, a survey of individuals knowledgeable in
ag-biotech indicated that they felt that potatoes and oilseed rape should be the lead targets.
The BioBridge study stated that, "there are indications that the effort being put into projects
in potatoes and oilseed rape outweighs the value of the crops. The number of projects for
wheat and barley seem disproportionately low, this may reflect the later development of
techniques for reliable transgenesis and regeneration of monocots or a reluctance of
industry to invest in the work."
BioBridge also looked at the beneficiaries of biotechnology applications in agriculture and
concluded that the consumer did not have the most to gain. A survey of thought-leaders in
academia and industry found that farmers, breeders, and agrochemical companies, in that
order, would be the major beneficiaries of transgenic crops with agronomic traits. Those with
the most to gain from transgenic crops with new quality/compositional characteristics would
be breeders, industrial processors, and food processors. Consumers ranked fourth in both
cases.
BioBridge concluded that although it may be true that European commercial
ag-biotechnology is playing catch-up to the United States, the gap will narrow in coming
years as more biotechnology- based crops reach EU markets.
Table I. EU field release and product development projects.
1. Prasher et al. 1992, Gene 111:229-233.
2. Prasher 1995, TIG 11:320-323.
3. Stewart, June 1996 Nature Biotechnology 14:682.
4. Chao et al. 1996, Nature 380:396-397.
UNC Greensboro
nstewart@goodall.uncg.edu
PLANT RESEARCH NEWS
TRANSGENIC GRAPES - ONE MORE HURDLE OVERCOME
Information Systems for Biotechnology
traynor@nbiap.biochem.vt.edu
(1) Ni, M., Cui, D., Einstein, J., Narasimhulu, S., Vergara, C.E., and Gelvin, S.B. (1995).
Plant J. 7, 661-676.
Center for Plant Biotechnology Research
Tuskegee University
prakash@acd.tusk.edu
Information Systems for Biotechnology
traynor@nbiap.biochem.vt.edu
ANIMAL RESEARCH NEWS
WOOLIER SHEEP
Virginia Tech
ewong@vt.edu
University of Arizona
INDUSTRY NEWS
REPORT ON EUROPEAN AGRICULTURAL BIOTECHNOLOGY
| Crop | Prod. Devel. | Field Rel. | Total |
| Oilseed Rape | 22 | 32 | 54 |
| Maize | 11 | 31 | 42 |
| Potato | 18 | 23 | 41 |
| Sugar Beet | 12 | 26 | 38 |
| Other Vegs | 22 | 7 | 29 |
| Ornamentals | 23 | 1 | 24 |
| Tomato | 5 | 14 | 19 |
| Wheat | 13 | 2 | 15 |
| Sunflower | 8 | 4 | 12 |
| Tobacco | 3 | 8 | 11 |
Source: European Crop Biotechnology - A Strategic Review & Directory. BioBusiness, April 1996, pg. 12.
References:
1. Ward, M. (Editor), Europe's agbio firms hide potential under a bushel? BioBusiness, Issue
20, April 1996, pg. 12-13.
2. European Crop Biotechnology, Volume 1: Status & Prospects- A Strategic View. Volume
2: A Directory of Crop Biotechnology Projects in the EU. Publications Department, BioBridge
Associates, 45 St. Barnabas Road, Cambridge, CB1 2BX, UK.
William O. Bullock
Institute for Biotechnology Information, LLC
Research Triangle Park, NC
PLANT TISSUE CULTURE INFORMATION EXCHANGE
Growing plants in test tubes is not perceived as being as glamorous as cloning genes, but
nevertheless plant tissue culture is an area of science which has been invigorated by recent
developments in plant molecular biology. Tissue culture is an essential prerequisite to the
development of transgenic plants because plant cells transformed with foreign genes have to
be regenerated into whole plants using tissue culture techniques. In addition,
micropropagation of horticultural plants is a multi-billion dollar industry worldwide and other
tools such as haploid production and embryo rescue are powerful techniques in crop
improvement.
Plant tissue culture also plays a significant role in crop germplasm conservation and
eliminating viruses from plants such as potato and cassava. Now there is a web site on the
Internet that claims to be "a virtual repository of virtually any type of information about in vitro
culture of plants." Plant Tissue Culture Information Exchange is on the Internet at
http://aggie-horticulture.tamu.edu/tisscult/tcintro.html. It is maintained by Daniel Lineberger
of Texas A&M University (dan-lineberger@tamu.edu).
The tissue culture web site has lot of useful information for the practicing tissue culture
researcher and teacher. An article by Mark Bridgen and John Bartok, University of
Connecticut, has numerous helpful tips on designing a tissue culture laboratory. Another
article by Dan Lineberger describes the many applications of plant tissue culture in crop
improvement. There are many useful links to other web sites such as the Society for In Vitro
Biology home page and the BIOSIS home page on commercialization of plant biotechnology
products, with descriptive information of transgenic crops and related intellectual property
issues.
There are many colorful pictures on "Impact of Biotechnology on Horticulture" which can be
viewed as slides. Other useful links include the Center for Soybean Tissue Culture and
Genetic Engineering and the Plant Tissue Culture Research at University of Minnesota,
which has a lot of information on crop tissue culture and transformation protocols.
Those who are interested in plant tissue culture research should also consider subscribing to
the plant tissue culture electronic discussion group. To subscribe, send an email message to
PLANT-TC@tc.umn.edu. Leave the 'Subject' line blank, and in the body of the message
type: sub plant-tc [your name].
C. S. Prakash
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Center for Plant Biotechnology Research
Tuskegee University
prakash@acd.tusk.edu
120 Engel Hall
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