In This Issue:
Report from Bt Forum
Symposium on Hybridization and Gene Flow Between Crops and Weeds
Canadian Patent Office Builds a Better Mousetrap
Report from Tuskegee Workshop
Tracking down a New Plant Defense Compound
AFLP Markers: A New Powerful Tool for Genome Analysis
Proteinase Inhibitor Protects Rice Against Insects
New Classification for Swine Pathogen
Biotechnology in Aquaculture
Aquatic Performance Standards Program Now Available
Microbial Genome Sequencing
Pigs to Provide Transplant Organs?
Access Excellence: A Web Site for High School Biology Teachers
About 130 researchers, growers, educators, crop consultants, and government officials attended a USDA-sponsored National Forum on Insect Resistance to Bacillus thuringiensis, April 15-16, in Bethesda, MD. The goal of the Forum was to share ideas and stimulate discussion about strategies for managing insect resistance to Bt.
In his welcoming remarks, USDA Under Secretary Karl Stauber said the Forum is especially timely because this year three transgenic crops (corn, cotton, and potatoes) are ready for large-scale planting in the United States. He said while Bt can provide an environmentally safe alternative to the use of chemicals, it is just as important to assure that Bt remains effective and reliable.
In the keynote address, Bruce Tabashnik, University of Hawaii, noted that most available evidence for resistance management is anecdotal. He emphasized that while models for resistance are fast, inexpensive, safe, and flexible, they are no substitute for rigorous field data. He said now is the time to develop a pro-active approach and develop substantive data on resistance.
The occurrence and management of resistance to synthetic pyrethroids was presented as a case study for managing resistance to Bt. Ian Watkinson, representing the Insecticide Resistance Action Committee, outlined the lessons learned from cooperative efforts by companies, extension, crop consultants, and growers. He spoke of the dilemma whereby support for a management program is most important at the very time when it is most difficult to achieve - before a problem develops; and if a problem diminishes, compliance quickly follows suit. He went on to offer a list of very practical recommendations for putting together an effective management plan that involves all the players.
Some participants expressed the view that Bt transgenic crops have undergone 10 years of research and testing, and offer a safe and effective alternative to chemically-treated crops. New genes are being discovered and new approaches that combine pest control strategies are being developed. Others expressed the opinion that "outrunning resistance" by sequentially substituting a new product when the current one becomes ineffective, is not the best course of action. Most agreed that more information is needed to build good pest management programs for both foliar applications as well as transgenic crops.
George Kennedy, North Carolina State University, zeroed in on the difficulties of implementation even when there is acceptance that resistance is a problem. Even with acceptance, there may be a tendency to try to outrun it, or to manage it on some theoretical basis. Acceptance that resistance is a problem doesn't ensure that a management plan will be adopted. Implementation of resistance management at the farm level depends on its advantage relative to alternatives, its complexity, and its compatibility with current practices. Is it homegrown or caused by others? What are the alternatives and what do they cost? What are the benefits? Complexity, or perceived complexity, reduces the relative advantage and leads growers to modify the management plan to make it simpler or more advantageous. Such modifications are likely to reduce the plan's effectiveness. Equally important, resistance management won't be adopted if it doesn't fit easily within existing operations. Kennedy described the ideal resistance management protocol as simple, invisible to the end user, and unmodifiable in its key elements. With an eye to the future, he noted that incorporation of multiple pest resistance traits and herbicide tolerance into Bt crops will lead to increased acreage planted to such crops and make it difficult to maintain adequate refugia for Bt susceptible populations.
In breakout sessions organized for corn, potatoes, cotton, and fruits and vegetables, participants were asked to identify the key components of a resistance management plan for the targeted crop, the hurdles to implementing the plan, how they could be overcome, and the follow up actions needed at the regional or national level.
In closing remarks, Deputy Under Secretary Cathie Woteki, said seven themes were apparent throughout the Forum. First, she said a majority of the participants agreed that Bt is one of U.S. agriculture's most valuable pesticides; second, it is important to prolong its usefulness; third, it's essential to continue research on insect resistance and management; fourth, we need better understanding of the economics involved in their use and production; fifth, more education will be needed; sixth, follow-up meetings will be necessary with USDA taking a leadership role; and seventh, responsibility for research, education, and monitoring will need to be shared. Wotecki said the proceedings of the Forum will be published and distributed widely.
Pat Traynor
Information Systems for Biotechnology
A Symposium on Wild-Crop Hybridization and the Ecological Impact of Escaped Transgenes will be held August 6, 1996 in conjunction with the annual meeting of the Botanical Society of America in Seattle, Washington. The purpose of the symposium, sponsored in part by the USDA, is to bring together botanists who study wild-crop hybridization and the evolutionary ecology of weeds. Gene flow from crops to free-living relatives is a relatively unexplored but potentially important mechanism by which weedy species can acquire beneficial traits.
For many crop species, little is known about the ability to cross spontaneously with related taxa, but genetic markers such as allozymes and RAPDs can be used to provide unambiguous evidence for flow and introgression. Recent studies suggest that transgenes will "escape" in a similar manner to other crop genes, thereby introducing traits such as strong resistance to disease, insects, frost damage, and herbicides into wild gene pools. A widely acknowledged risk associated with transgenic crops is the possibility that hybridization with weedy relatives (or naturalization of the crop itself) will cause novel, fitness-related transgenes to result in the rapid evolution of more invasive weeds.
Topics on this and related issues include:
For information, contact Allison Snow, Ohio State University, 614-292-3445; snow.1@osu.edu.
The Wall Street Journal highlighted the commercial interest in transgenic animals in a recently published article on Grace, a goat altered to produce a therapeutic protein in her milk (April 9, p. B1). This focus on generating protein pharmaceuticals in transgenic animal milk is reflected in the establishment of numerous "biopharming" programs to produce therapeutic proteins such as anti-thrombin III, Factor IX, Factor VIII, protein C and tissue-type plasminogen activator. Are transgenic animals like Grace patentable? The answer depends upon the particular country in which you attempt to obtain patent rights.
In the United States, the threshold requirement for patentability is that the claimed invention must be a "new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof" (1). Similarly, section 2 of the Canadian Patent Act defines a patentable invention as a "new and useful art, process, machine, manufacture, or composition of matter, or any new and useful improvement in any art, process, machine, manufacture, or composition of matter." Although the language in both statutes is virtually identical, a transgenic animal is patentable in the United States, but not in Canada.
This point is best illustrated by the fact that, on April 12, 1988, Harvard researchers Philip Leder and Timothy A. Stewart obtained their U.S. patent for transgenic non-human mammals that have cells containing a recombinant activated oncogene sequence (2). Meanwhile, the Canadian counterpart of the "OncoMouse" patent still has not been issued. In fact, the Canadian Patent Office (CPO) recently upheld an examiner's rejections of Leder and Stewart's claims to transgenic non-human mammals. Why has the OncoMouse patent enjoyed eight years of patent protection in the United States, while its Canadian cousin is still struggling through patent prosecution? It depends upon an interpretation of the terms "composition of matter" and "manufacture."
The scope of patentable subject matter is very broad under U.S. law. A justification for an expansive viewpoint can be found in the Committee Reports accompanying the 1952 Patent Act which show that Congress intended patentable subject matter to include "anything under the sun that is made by man" (3). The Supreme Court, however, has placed some limits on suitable subject matter, holding that laws of nature, physical phenomena and abstract ideas are not patentable. The rationale for excluding these things from patent protection is that they are not the result of inventive, creative, human action, which is the type of activity that the patent laws are designed to encourage.
Although Louis Pasteur managed to obtain a U.S. patent for yeast in 1873, an in-depth evaluation of whether U.S. patent law should protect a life form began about 100 years later with Ananda M. Chakrabarty's invention of a new microorganism. Chakrabarty, a research microbiologist at General Electric Co., developed a strain of bacteria that could degrade two or more components of crude oil due to the presence of foreign plasmids. Chakrabarty filed a patent application containing claims to the new bacteria, which the U.S. Patent and Trademark Office (USPTO) examined with mixed enthusiasm.
In 1980, however, the U.S. Supreme Court ruled that Chakrabarty's microorganisms could be patented (4). The Court decided that a new, human-made single-celled organism can be patentable subject matter under section 101 as a "composition of matter" or as a "manufacture." The important point was that the claimed bacteria were not "nature's handiwork," but the product of the inventor.
Eventually, the USPTO decided that U.S. law should provide protection for new forms of multicellular organisms, including plants, oysters and transgenic mammals. In short, a living organism can be considered as patentable subject matter in the United States if the organism is a nonnaturally occurring product of human ingenuity.
The CPO, however, has decided not to follow the U.S. Supreme Court's expansive definitions of "manufacture" and "composition of matter." According to the CPO, these terms apply to something that is made under the control of the inventor and is reproducible in a consistent manner.
In the case of the OncoMouse application, the CPO found that the intervention of the inventors only ensured that reproducibility extended as far as the cancer-forming gene, and that the inventors do not have full control over all characteristics of the resulting mouse. Thus, the CPO concluded that a non-human transgenic mammal does not fall within the definition of "invention" under Canadian patent law. Harvard University, the assignee of the Leder and Stewart patent application, is appealing the CPO's decision to the Federal Court of Canada.
A reversal of the CPO's decision would not necessarily mean that the CPO will rush to grant numerous transgenic animal patents. As of last fall, the USPTO had granted only 11 animal patents (nine mice, one rabbit and one worm), though there were 461 pending applications with at least one claim to an animal.
References
1. 35 U.S.C. Section 101
2. U.S. patent No. 4,736,866 (1988).
3. 1952 USCCAN (S.Rep.No.1979) 2399.
4. Diamond v. Chakrabarty, 206 USPQ 193 (1980).
Phillip B.C. Jones
Foley & Lardner, Washington, D.C.
pbc@ari.net
The Center for Biotechnology Research at Tuskegee University held a "Workshop on Transgenic Plants: Biology and Applications" earlier this month. The workshop sought to enhance minority participation in plant molecular biology by providing a forum for presentations of the newest developments in transgenic plant research and an opportunity for young scientists to establish professional networks. The workshop included lectures from eminent scientists on the current status of research, a panel discussion on federal funding opportunities, special internet demonstrations, posters, displays from companies and commercial vendors and recruiting information from numerous graduate programs.
One of the highlights was a panel discussion which addressed the problem of minority participation in biotechnology. The seven person panel chaired by Dr. William Gordon (Howard University) represented a cross-section of scientists at different professional levels. The panel addressed the obstacles most likely encountered when recruiting minorities. One common theme was the negative perception that agriculture-based research has. As noted by Jacquelyn Jackson (Tuskegee University) most undergraduates, particularly minorities, wonder "what can be done with a degree in agriculture, except drive a tractor." Several speakers stressed that university and even high school students need to be exposed to the breadth of career opportunities biotechnology and plant sciences offer.
In order to increase minority recruitment Dr. Jerome Roberts (Alabama A&M University), suggested that agriculture-based research improve its public relations with the minority community. Recruitment efforts need to start early, in high school - if we wait until these students are junior or seniors in college the probability of attracting them into plant science is marginal. How do we increase the odds? A conference such as the Tuskegee workshop is a good start, but in some regards is like "preaching to the converted". Most of the minority participants had already decided that plant research is a viable option. Just as Westinghouse holds scholarship competitions for young inventors, perhaps the plant research and biotechnology community should try a similar approach to identify talented minority students and encourage them to build a career in science.
Full proceedings from the workshop, which was supported by grants from the National Science Foundation and the U.S. Department of Agriculture, can be obtained from the following website address: http://www.tusk.edu/tusk/agriculture/workshop/wrkshop.htm or by contacting Dr. C.S. Prakash, School of Agriculture, Tuskegee University, Tuskegee, Al. 334-727-8023; fax: 334-727-8552; prakash@acd.tusk.edu.
Camellia Moses Okpodu
Virginia Tech
Cytokinin, a multipurpose plant growth regulator that influences numerous physiological processes, may lead researchers to a naturally produced compound that protects plants from insect pests. USDA/ARS researchers at the Plant Molecular Biology Lab in Beltsville, Md. are tracking down a secondary metabolite that shows up in transgenic plants that overproduce the hormone. The scientists engineered tomato and tobacco plants with a cytokinin gene from Agrobacterium tumefasciens, under the control of a wound-inducible promoter found in potato tubers. In response to insect damage, cytokinin expression goes up, reaching a maximum within 8 to 24 hours of up to 70 times the normal amount of hormone. Levels then drop off by 48 hours.
Leaves from transgenic plants were less palatable to chewing and sucking insects, causing them to eat less and affecting maturation. Tomato hornworms ate 60 percent less than control insects fed nontransgenic leaves; newly hatched green peach aphids suffered higher mortality on the transgenic leaf diet. Compared with controls, only half as many aphids reached adulthood and their reproductive ability was decreased.
The ARS group headed by Ann Smigocki is close to identifying the active compound. Using bioassays developed by ARS colleague John Neal, they have narrowed the search down to a purified fraction that contains only two secondary metabolites. Nuclear magnetic resonance studies may resolve which is active against insects. In addition to lepidopterans and hymopterans, representative species from other insect Orders are being tested to characterize the compound's range of activity. Collaborative projects are underway to insert the modified cytokinin gene into sugarbeet, soybean, alfalfa, strawberry, and fescue. USDA/ARS holds a patent on the gene and expects to patent the active compound once it has been identified.
Pat Traynor
Analysis of plant and animal genomes using DNA markers is proving valuable in breeding programs to rapidly develop improved crop and livestock strains. Genome studies giving scientists insight into the organization of plant and animal genomes are also laying the groundwork for a multitude of practical applications. Variety identification through DNA fingerprinting, development of genetic maps to facilitate indirect selection of economic traits such as disease resistance without cumbersome screening, cloning of important genes, and evolutionary and phylogenetic studies are all enhanced by genome analysis.
The three principal approaches for identifying polymorphic DNA markers until now are Restriction Fragment Length Polymorphism (RFLP), Random Amplified Polymorphic DNA (RAPD) and microsatellites. All three approaches have certain merits but also a few inherent disadvantages. RFLP is a laborious technique that relies on Southern blotting and results in the detection of a small number of alleles; RAPDs are sensitive to reaction conditions and thus known to have problems of reproducibility. Microsatellites provide high polymorphism but require lengthy studies involving cloning and sequencing in each species to obtain information on flanking nucleotide sequences.
The new approach, AFLP (amplified fragment length polymorphism), overcomes some of the disadvantages of the earlier techniques and is thus quickly becoming very popular among agricultural scientists as a versatile and powerful tool in genome analysis. A major reason for the rapid acceptance of AFLP technology is its ability to detect a large number of polymorphic DNA markers rapidly and in a reproducible manner. The procedure was developed by Keygene, a private company in Netherlands led by Dr. Marc Zabeau, which holds the patent for the technology.
The AFLP approach is conceptually simple. The procedure draws from both the RFLP and PCR techniques in that genomic DNA is cut with restriction enzymes and the resulting millions of fragments are reduced to a hundred or so detectable bands on a gel using two rounds of PCR (1). Unlike RFLP analysis however, AFLP involves the detection of the presence or absence of restriction fragments rather than differences in their lengths.
In the procedure, DNA is digested with two enzymes, a rare-cutter (e.g., EcoRI) and a frequent-cutter (MseI); oligonucleotide adapters are then ligated to ends of the fragments. Using primers corresponding to the ligated adapters, only those fragments with EcoRI and MseI sites at either end are PCR amplified. This initial amplification will select a subset of the fragments which is further reduced to a manageable number through a second round of selective amplification. The second amplification uses primers corresponding to the sequence of the adapter + restriction site bases, plus the first few (one to five) nucleotides of the restriction fragment itself. One extra (selective) nucleotide on each primer will match only one of the four possible nucleotides (A, T, G or C) and thus results in the amplification of only one in sixteen double stranded fragments. The use of two selective bases will decrease the number by 1/256. An average-sized plant genome like soybean amplified with three selective bases on each second round primer will produce about 120 fragments which typically are detected on sequencing type polyacrylamide gels through radioactive labeling.
The primary reason for the superiority of AFLP approach is that it detects a very large number of DNA bands enabling identification of many polymorphic markers. Routinely about 50-100 bands are observed in each lane of a AFLP gel, compared with about two to five bands obtained in an RFLP analysis or five to ten bands with the RAPD technique. AFLPs detect more point mutations than RFLPs and are simpler than microsatellites as no prior sequence information is needed. The AFLP does not necessarily offer higher rates of polymorphism but is more efficient in detecting such variation and thus amenable for high throughput screening.
AFLPs enable rapid creation of very high density genetic maps. For instance, in barley with a large genome size and a low polymorphism rate, the use of AFLP analysis enabled development of a more informative and enriched genetic map (2). Jonathan Jones and colleagues at John Innes Center in England have recently employed AFLP to identify many DNA markers tightly linked to the tomato gene for resistance to the leaf mold pathogen (3).
Similarly, Christiane Gebhardt's group at Max Planck Institute in Germany have identified 29 AFLP markers linked to the R1 gene for resistance to late blight disease and two markers for resistance to the root cyst nematode in potato (4). Marc Van Montagu and associates at Gent University in Belgium have identified markers linked to leaf rust resistance in poplars using this approach. AFLPs are proving useful for positional cloning of genes as PCR screening of YAC (yeast artificial chromosome) or BAC (bacterial artificial chromosome) libraries facilitates easier identification of such genes. Further, an adaptation of AFLP to screen mRNA populations will enable identification of those genes that are differentially expressed and this will also facilitate rapid cloning of important genes.
Although the AFLP approach is highly informative, a few criticisms of this technique are in order. It requires the use of multiple procedures in the protocol, making it expensive, cumbersome and laborious. The use of radioactivity to detect DNA in AFLPs is a major drawback that may limit its use, however Guohao He at the Center for Plant Biotechnology Research at Tuskegee University and Susan McCouch at Cornell University have adapted non-radioactive silver staining protocols to detect DNA fragments in AFLP gels with no major loss in sensitivity. Image analysis software is also being developed by Keygene to analyze the complex AFLP patterns as they are difficult to interpret visually. Reagents and kits for AFLP analysis is available from GIBCO BRL Life Technologies (Gaithersburg, MD) and Perkin Elmer Applied Biosystems (Foster City, CA). A detailed protocol is on the Internet at http://carnegiedpb.stanford.edu/methods/aflp.html.
References
1. Vos, P. et al. (1995). Nucleic Acids Research 21: 4407-4414.
C. S. Prakash
When attacked by insects, some plants produce insecticidal proteins as part of their natural defense
response. Wounding caused by insect damage can induce plants to synthesize lectins, -amylase inhibitors,
proteinase inhibitors, or other compounds intended to help ward off the attack. With a little help from plant
scientists, the strategy soon may be adopted by a wider variety of important crop species. For example, Ray
Wu and colleagues from Cornell University and Zhejiang Agricultural University in Hangzhou, China have
engineered rice plants with a potato proteinase inhibitor gene, and shown that the plants are resistant to pink
stem borer (Nature Biotechnology, April 1996).
Proteinase inhibitors are a class of defense proteins that work by inhibiting enzymes in the predator's
digestive system, so that feeding slows or stops and further development is delayed or arrested. Their utility
as protective transgenes was established in earlier experiments with tobacco. Rice plants were engineered
to express the potato proteinase inhibitor II gene (pin2) under the control of its own promoter teamed up
with the first intron of the rice actin 1 gene. This promoter-intron combination has been shown to drive
high-level, wound-inducible expression of foreign genes in transgenic rice plants. The transformation
plasmid also carried the herbicide resistance bar gene linked to the CaMV 35S promoter, allowing
transformants to be selected on the basis of resistance to phosphinothricin.
Fifth generation plants of two primary transgenic lines and two transformation-derived nontransgenic lines
were assayed for pink stem borer resistance. Rice stem borer damage is visible as seedless dead panicles,
called whitehead. In the bioassay, four second instar larvae were weighed and placed on plants at early
heading stage. Five weeks later, tillers showing whitehead symptom were counted and the larvae were
weighed again.
Over both lines, at least 70% of the tillers on nontransgenic control plants showed the whitehead symptom;
larvae had increased their weight 3-4 fold and developed to the fourth or fifth instar stage. Less than 18%
of the tillers on plants expressing the pin2 gene showed whitehead; larvae showed little weight gain and
were still in the second-third instar stage.
Transgenic rice expressing a proteinase inhibitor gene joins other rice lines successfully engineered for
insect and disease resistance. Breeders now have available lines expressing a Bt -endotoxin gene or a viral
coat protein gene conferring resistance to rice stripe virus.
Pat Traynor
African swine fever has been the scourge of swine producers in many parts of the world. The disease has
come as close to the U.S. as the islands of the Caribbean, but apparently has not yet been found in this
country. The causative agent, African swine fever virus, is among the exotic pathogens garnering the most
attention from governmental regulatory officials and swine producer groups in the U.S.
Now, a complete genome sequence has been reported for the virus. It contains just over 170 kilobase pairs
and more than 150 open reading frames. There are five gene families, proteins which are apparently
membrane-associated or secreted, and enzymes for nucleic acid and protein metabolism. Genes which may
be involved in virulence, including persistence, were also identified. In the past, it was believed that African
swine fever virus was an iridovirus, although more recent taxonomic analysis suggests that it is intermediate
between poxviruses and iridoviruses. Sequence data support the latter position, placing African swine fever
virus in an independent family.
J. Glenn Songer
The worldwide importance of aquaculture is enormous, from the standpoint of food production and
generation of income. Disease caused by bacteria, viruses, and protozoa remains a major hurdle to
economical production of many marine invertebrates. Ongoing work to prepare transgenic shrimp and
molluscs is therefore of major importance. Transformation of these two groups has been demonstrated,
including expression of genes from "foreign" promoters. Although the field lags far behind other animal
transgenics, it seems likely that it will be possible to produce disease-resistant shrimp and mollusks in the
foreseeable future.
A more immediate approach is the application of biotechnology to rapid and simple disease diagnosis.
There is an increasing variety of reagents and materials available, and many have shown great promise.
Molecular probes, used in conjunction with a well-defined diagnostic scheme and attention to management,
will likely have major impact on profitability of the aquaculture industry in years to come.
J. Glenn Songer
The computerized version of the Performance Standards for Safely Conducting Research with Genetically
Modified Fish and Shellfish is now available on diskette and the internet. The DOS-based software presents
information in the two-volume Performance Standards as a series of questions designed to identify and
manage risks associated with research with finfish, crustaceans, and mollusks. The Performance Standards
were developed under the auspices of the Agricultural Biotechnology Research Advisory Committee and
have been endorsed by USDA. The computer program, developed by Information Systems for
Biotechnology (ISB), has an easy-to-use format that allows users to select answers and type in responses,
then generate a report suitable for review by a biosafety committee.
Beyond its usefulness in aquatic biotechnology, the computer program serves as a model for risk
assessment - risk management protocols that evaluate the environmental consequences of releasing
genetically modified organisms. Having designed the software to be easily modified for application to other
organism groups, ISB is interested in exploring the potential utility of formulating analogous standards for
other types of transgenic organisms. The intent is to provide guidance and support to the research
community and anyone having an interest in the environmentally responsible use of genetically engineered
products.
To download a copy of the program (available as a .zip file or self-extracting .exe file) use www, gopher,
or ftp as explained at the end of the News Report to download "gmfish10.zip" or "gmfish10.exe". To
request a diskette copy of the "gmfish program", send email to nbiap@vt.edu or call 540-231-3747. Printed
copies of the Performance Standards are also available while supplies last.
Doug King
Funding has been approved for work which will lead to sequencing the genomes of three bacteria (an
archaebacterium and either two eubacteria or one eubacterium and a cyanobacterium). This work, funded
by the Department of Energy, is motivated in part by the demand for microorganisms with specific
characteristics useful in applied settings. High on the list of potential applications is bioremediation of
contaminated sites having extreme environmental conditions, such as deep oil wells and other high-temperature and high-pressure environments. Alternatively, bacterial metabolism of contaminants may give
rise to desirable products such as industrial chemicals or, perhaps, alternative fuels.
One of these organisms, Thermotoga maritima, has been the subject of intense study due to the fact that
it is a hyperthermophile. Sequencing efforts to date have shown that most sequence tags correspond to
proteins previously identified from other organisms. For example, cloning and sequencing of the trp operon
revealed that the trpE transcript overlaps a second transcript which is a fusion of trpG and trpD, making
it similar to E. coli and Salmonella typhimurium. Comparison of the deduced amino acid of the genes in
this operon with those cloned and sequenced from other organisms revealed that they were more similar
than expected.
The overall scientific value of the work will be considerable. Bacterial genome sequencing will provide
general information on genome structure and organization, and make important contributions to our
understanding of the origin of bacteria as life forms and their evolution to modern times. Furthermore, the
sequencing effort will help drive the evolution of new methods for generating and manipulating sequence
data. In addition to basic scientific and industrial benefits, there will likely be medical benefits as well.
J. Glenn Songer
One of the many impacts that biotechnology has had on society has been to expand the interrelationships
between agriculture and medicine. Examples include the use of molecular biology to identify plant
molecules with medicinal value and the use of transgenic crops and animals as pharmaceutical factories.
Genetic engineering is also playing a major role in the utilization of animals, specifically pigs, as potential
sources of organs for human transplant. A recent report by analyst Peter Laing of Salomon Brothers
suggests that the first regulatory approvals for the use of animal organs as human transplants
(xenotransplantation) could come as soon as the year 2000 (1).
Pigs are the animal of choice for xenotransplantation because of adequate anatomical and physiological
similarities to humans, the fact that porcine (pig) tissue grows in the presence of human growth hormones,
the ability to breed large litters relatively quickly, and the likely decrease in ethical objections to the use of
pig organs verses other animals.
The need for xenotransplantation stems from the lack of adequate human donor organs. The Salomon
report notes that 160,000 new cases of heart disease are diagnosed each year that could be best treated
through transplantation, but at the end of 1994 only 2,900 met the criteria for acceptance to the waiting list
and only 2,300 heart transplants were carried out that year in the U.S. The situation is essentially the same
for other organs. This level of need translates to substantial potential markets for companies working to
advance successful xenotransplant strategies.
One estimate puts the potential market for xenotransplantation at $6 billion by the year 2010. Current
players developing the technology include Imutran (United Kingdom), Nextran (Princeton, New Jersey),
Alexion (New Haven, Connecticut), and Biotransplant (Boston, Massachusetts). The general strategy being
pursued by these companies is to genetically engineer the cells of the animal's organs to express proteins
that minimize hyperacute immune rejection by the human recipient.
Imutran is anticipating beginning its first human feasibility studies sometime in 1996 using organs from
transgenic pigs expressing a human immune system complement activation inhibitor. If these and other
trials succeed, and xenotransplantation begins to realize its potential, it is estimated that Imutran would
supply its partner, Sandoz, with pig organs at a fixed unit price, and Sandoz would distribute the organs
to transplant centers at an estimated cost of $12,000 per organ. Sandoz also stands to gain from the success
of xenotransplantation in that transplant patients require immunosuppressive drugs, leading to the potential
market growth of Sandoz' Sandimmun and its successor Neoral from 1994 sales of $1 billion to over $5
billion in 2010 (1).
Although it is thought that the use of pig organs would decrease the opposition to using animal organs for
transplantation, there are still a number of issues that need to be addressed. A recent report issued by the
London-based Nuffield Council on Bioethics addressed the ethics of animal-to-human transplants. The
report concluded that "the risks associated with the possible transmission of infectious disease as a
consequence of xenotransplantation have not been adequately dealt with. It would not be ethical, therefore,
to begin clinical trials of xenotransplantation involving humans" (2). Given the need and market potential,
if the technology works, these and other issues will likely be addressed and the Salomon report's
prognostication that "there is a high probability that xenotransplants will become routine in the early years
of the next decade" will move closer towards reality.
References:
1. Financial Times Biotechnology Business News, April 10, 1996, Vol. 6, Issue 123, pp. 12 -16.
2. Nature Biotechnology, April 1996, Vol. 14, No. 4, pp.403-404.
William O. Bullock
If you are a high school biology teacher or even a college instructor, you probably are looking for some
innovative ideas to creatively teach your students. Or perhaps you wish to know what other methods
teachers around the country are using to teach the polymerase chain reaction (PCR) technique, dinosaur
paleontology or genetic counseling. If so, then a visit to the "Access Excellence" site on the Internet's world
wide web is in order. Access Excellence (http://www.gene.com/ae/) is an educational network funded by
Genentech, Inc., the biotechnology company, which brings together many high school biology teachers
from around the country and provides them with valuable resources to share ideas for innovative
instruction including articles on class room exercises, profiles on scientists, graphics and information on
biotechnology education and career resources.
Be sure to visit the "Activities Exchange" section where the favorite class room activities of high school
teachers (along with pictures of these teachers) from around the country are posted on topics such as
antibiotic production, bioethics, transgenics (can some one make a cow that produces chocolate milk?),
using jewelry to teach DNA codon usage, Genes-R-Us (on genetic counseling), "Transcription-Translation
Tango" to teach the intricacies of protein synthesis, and many other gems. A hot link to the "DNA Learning
Center" of the Cold Spring Harbor Laboratory lets you learn the use of PCR to estimate gene frequencies
with Alu markers. In the "Activities-To-Go" section, there are text and graphics files on many interesting
subjects such as DNA sequencing, DNA fingerprinting, AIDS, Jurassic Park Study Guide and scientific
clip art.
An in-depth look at biotechnology can be found at the "About Biotech" section, which has narratives on
the history of biotechnology and its current applications in farming, medicine and the environment. My
favorite part here is the "Pioneer Profiles" which has brief biographies of scientific luminaries such as
Barbara McClintock, James Watson, Kary Mullis and Linus Pauling. "The Story of DNA" has a lucid
chronicle of the discovery of the structure of DNA. The rich hypertext format is used throughout the site
and these hot links let you jump around related topics. For instance, while reading about "PCR", you can
jump to "Kary Mullis", its discoverer and then to "DNA" and so on. An interview with Dr. Francis Crick,
the co-discover of DNA structure is a 'must-visit' page of Access Excellence. The Human Genome Project
and many of its ethical issues receive considerable attention at various locations at this site. The "Career
Center" provides addresses of various biotechnology related institutions around the country and
descriptions of careers in biotechnology. Addresses of U. S. institutions in all 50 states providing higher
education in biotechnology can also be found here.
A visit to the "Teachers Lounge" lets you listen to the discussions among teachers where you can also post
messages. The "Teacher-Scientist" Network has eminent scientists delivering on-line seminars on specific
topics such as the current one "Microbial Fermentation-Changing the Course of Human History". The
"Graphics Gallery" has an excellent downloadable collection of cartoons and diagrams that are useful in
teaching varied topics such as chromosome crossing over, DNA restriction digestion, PCR, transgenic mice
and viral replication. The "What's News" contains science news, interviews with scientists, factoids and
information on science programs in television, radio and the Internet.
Whether you are a novice or a professional in biotechnology, the Access Excellence on the web is bound
to interest you and deserves a bookmark in your browser for repeat visits.
C. S. Prakash, Tuskegee University
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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.
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ISB News Report
2. Becker, J. et al. (1995). Mol Gen Genet 249: 65-73.
3. Meksem, K. et al. (1995). Mol Gen Genet 249: 74-81.
4. Thomas, C. et al. (1995). The Plant Journal 8: 785-794.
Center for Plant Biotechnology Research
Tuskegee University
prakash@acd.tusk.edu
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