Cloning and Genetic Engineering of Agricultural Animals and the Need for Research Funding

1
Cloning and Genetic Engineering of Agricultural
Animals and the Need for Research Funding

• Ron Stotish, Aqua Bounty Technologies
• Leah Wilkinson, ViaGen
• Barb Glenn, BIO
• Presentation to USDA, CSREES
• June 17, 2009

2
Agenda

• Introduction
• Status of the industry
• Research and development the pipeline
• Domestic and global regulation
• What do consumers think?
• Public communication and education
• Future research needs

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21st Century Problems

• Increasing Population
• 9 billion by 2050
• At present, 963 million malnourished
• Improved Nutrition in China and India
• Double food needs
• Water Shortage
• Aquifers being depleted
• Livestock cause 19 of environmental degradation
• Global meat demand is projected to double by 2050

4
Todays Agriculture

• Importance of investment in science and
  technology for ensuring food security in the long
  term.. UN Food Conference, June 2008
• In the long term, we believe sustainable food
  security will come from advances in science and
  technology and the creation of an efficient
  global market for both agriculture products and
  food production technlogies.- Deputy Secretary
  of State John Negroponte, World Food Prize
  ceremony, June 13, 2008

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Todays Agriculture

• The issue of chronic hunger and food security is
  at the top of the agenda The Obama
  Administration is committed to providing
  leadership in developing a new global approach to
  hunger.
• a system of agriculture that nourishes all
  humankind requires more than a single
  breakthrough or advances in a single field. It
  requires a sustained and comprehensive approach.
  We need to create a global supply chain for food.
  Today, that chain is broken, and we need to
  repair it and make it stronger.
• --Hillary Rodham Clinton, June 11, 2009,
• Remarks at the 2009 World Food Prize
  Announcement

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Todays Agriculture

• We seek a world without hunger. Our objective
  is to build sustainable agriculture systems so
  all people have reliable access to nutritious
  food.
• six key principles that will guide our future
  efforts
• Support sustainable solutions to hunger We seek
  strong and sustainable agriculture sectors that
  produce and deliver food efficiently. From local
  scientists that design new technology to farmers
  that profit from their hard work.
• Adopt a comprehensive approach.Expand knowledge
  and training including support for research.
• --One Table Advancing Agriculture to End
  Hunger,
• June 10, 2009, Fact Sheet during the 2009 World
  Food Prize Announcement

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Todays Livestock Industry

• Use assisted reproductive technologies
• Share genetics between parents
• Slow advancement
• Technology adopters

25 Years of Conventional Improvement (photo by
PIC)
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Omega/Skim Dairy Cow

• The 2005 Dietary Guidelines for Americans
  recommended
• Consumption of 8 oz of fatty fish/week 416
  oz/year 26 pounds/year
• When selecting and preparing meat, poultry, dry
  beans, and milk or milk products, make choices
  that are lean, low-fat, or fat-free
• Limit intake of fats and oils high in saturated
  and/or trans fatty acids, and choose products
  low in such fats and oils

Fast Fact
Marge A dairy cow in New Zealand that produces
naturally skim milk and high levels of Omega-3
oils.
Consumers lack 1/3 of the recommended intake of
Omega 3
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Solutions!

• There is only one technology likely to deliver
  and that is genetic modification (GM).- UK
  Government Former Chief Scientific Advisor Sir
  David King, The Financial Times, July 7, 2008
• To this end we will accelerate research and
  development and increase access to new
  agricultural technologies to boost agricultural
  production we will promote science-based risk
  analysis including on the contribution of see
  varieties developed through biotechnology G8
  Leaders Statement on Global Food Security, July
  8, 2008

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Solutions!

• to bring about sustainable change.Science and
  Technology It is essential that science be
  affirmed as the primary vehicle of change for
  economic development. The successes of U.S.
  agriculture, the Asian Green Revolution, and the
  few nuggets of change in Africa are evidence that
  science-based development offers not only a way
  out of hunger and poverty, but also leads to
  prosperity. Life altering changes will continue
  to require scientific innovations that raise
  productivity and income. Recent advances made in
  the biological sciences offer exciting
  opportunities for addressing some of the most
  intractable agricultural problems prevalent in
  the tropics. - Dr. Gebisa Ejeta, 2009 World
  Food Prize recipient. March 24, 2009

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Technology is Crucial
Over the next 50 years, the worlds farmers and
ranchers will be called upon to produce more food
than has been produced in the past 10,000 years
combined, and to do so in environmentally
sustainable ways. -Jacques Diouf, FAO
Director General, 2007
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Technology is Crucial
70 percent of the worlds additional food needs
can be produced only with new and existing
agricultural technologies. -United Nations
FAO, 2002
13
Animal Biotechnology Animal Well Being and Care
are Top Priorities

• Healthy animals produce healthy foods.
• In addition to meeting science-based domestic and
  international regulatory requirements, the
  industry will work proactively on adherence to
  good stewardship principles that promote animal
  care and well being.
• Build stakeholder and public confidence

14
BIOs Statement of Ethical Principles for the
Care and Use of Animals in Biotechnology Research

• Humane treatment of animals
• Judicious use of animals
• High standards of care
• Regulatory oversight
• Increased public awareness
• Open discussion of ethical considerations

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Cloning of Agricultural Animals

• Status of the industry
• Research and development the pipeline
• Domestic and global regulation

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Recent U. S. GovernmentRegulatory Progress on
Cloning

• FDA finalizes Risk Assessment (Jan. 2008)
  concluding that foods are safe
• USDA leads transition, cloning is being adopted
  and progeny may enter market place
• USDA continues the voluntary with holding of
  animal clones from the market place

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What is Cloning?

• An Assisted Reproductive Technology
• Another tool in the toolbox
• Artificial insemination
• Embryo transfer
• In vitro fertilization
• Somatic cell nuclear transfer
• Creates genetically identical twins
• Identical twins separated in time

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Keep in mind

• Cloned animals are NOT Genetically Modified
• Progeny of cloned animals ARE NOT clones
• Cloned animals will be rare in food supply
• Clones are breeding animals

Pigs cloned from show pig Miss Pauline
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Cloning Solutions

• Product Attributes
• Low fat, high Omega 3 milk
• Pro-environment
• Increased feed efficiency
• Reduce water consumption
• Reduce waste stream
• Animal health and welfare
• Disease resistance
• Reduce antibiotic usage
• Preserve Superior Genetics
• Support biodiversity

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Preserve Superior Genetics

• Post-disease outbreak
• Insurance against loss of genetic progress
• Neutered animals
• Produce genetically identical studs to
  top-performing steers, barrows and geldings
• Endangered species - Prevent extinction of
  endangered species

Angus heifer calf-- Clone of a dam with proven
genetics. Donor cow is 10 years old and nearing
end of reproductive life.
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Supply Chain Management

• Consumer Choice
• Industry Support

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Supply Chain Management

• Clone Registry
• RFID ear tags
• Database
• Query based
• Marketing Incentive
• 2x market value
• Refundable deposit
• Verify disposal
• USDA Process Verified

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Research and Development Industry

• Focus is on commercialization
• Efficiency, quality of embryos, and animal health
• Nuclear reprogramming
• Pre-implantation screening
• Post-implantation monitoring
• Longitudinal studies

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Research and Development Global

• Academic research continues worldwide
• 185 peerreviewed papers from Jan. 2008 to April
  2009
• 21 different countries
• Only 30 papers from U.S. scientists
• 3 were ViaGen papers

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International Acceptance

• New Zealand
• Europe
• Japan
• Canada
• Argentina
• Brazil

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• Codex Alimentarius Commission
• Declined to include cloning with regard to safety
  of foods derived from biotechnology because it is
  not under the definition of modern biotechnology
• World Organization for Animal Health (OIE)
• Guideline on health of animal clones and
  surrogates
• International Embryo Transfer Society (IETS)
• Developed a paper on health of animal clones
• Developing a publicly available database on
  composition of food products from clones and
  offspring

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Genetic Engineering of Agricultural Animals

• Status of the industry
• Research and development the pipeline
• Domestic and global regulation

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What is Genetic Engineering of Agricultural
Animals?

• Animal biotechnology
• The deliberate modification of the animal genome,
  in contrast to spontaneous mutation.
• Innovative technology that will transform public
  health
• Genetic engineering (GE) allows expression of
  desirable traits in agricultural animals that
  benefit human kind.

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Benefits of Genetic Engineering

• Enhancing food quality and safety
• Softer environmental footprint
• Enhanced animal health and welfare
• Advancing human health

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AquAdvantage Salmon
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AquAdvantage Salmon Product Definition
An Atlantic salmon (Salmo salar) from the EO-1a
line with one copy of the a-form of opAFP-GHc2 at
the a-locus
that grows to a mean body weight of
100 g within 2700 deg-days of first-feeding
and will be commercially available as
eyed-eggs for cultivation of triploid, monosex
fish in physically-contained, freshwater
production facilities.
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AquAdvantage Broodstock Program

• What is it?
• Egg to Harvest in half the time
• 1st Feed to smolt in less than 110 days
• How does it work?
• A change in the regulation of one
• gene to allow the fish to produce GH year around
  
• No change in composition, physiology, or
  behavior of the Atlantic Salmon, except for
  faster growth in the first year

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Growth Hormone Transgenesis
Regulatory sequences from ocean pout AFP gene
coding domain from chinook salmon GH-1 cDNA
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AAS Growth Performance
Transient increase in specific growth rate during
early-life
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Detection of the EO-1a Transgene
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Durability of Phenotype Genotype
Molecular-genetic integrity of the transgene
heritability of the AquAdvantage phenotype have
been confirmed over seven generations
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Basis of Prospective NADA Approval
Claims
Food Safety
Durability
Phenotype
Integrated Transgene
Plasmid Transgene
Product Definition
? Integration event ? Performance level ?
Production condition
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Commercial Production Operations
ApprovedGrow-Out Harvest
Production of Triploid, Monosex, Eyed-AAS Eggs
Sale
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AquAdvantage Salmon
Originally developed as a superior production
animal
Todays farmed Atlantic Salmon Industry Sea
cage based production under environmental
pressure Water quality Infectious disease
Escapes Geographically localized
Can the characteristics of AAS address these
issues ?
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AquAdvantage Salmon Growth rates permit
harvest in approximately half the time Growth
rates allow economic production in contained
facilities Contained production, redundant
biological and physical containment a. reduced
disease exposure b. no interaction with wild
populations or ecosystems c. regional production
with reduced transportation Offers the
possibility of a smaller environmental
footprint
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AAS Development Program Biology and
Microbiology Molecular biology and
genetics Biochemistry and Physiology Nutrition Inf
ectious Disease and Epidemiology Pathology Animal
Behavior Ecology and Environmental
Sciences Analytical Chemistry Statistics
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The Enviropig

• Pork The worlds most widely eaten meat. 43
  eat pork 23 beef 27 chicken.
• Japan, China, Mexico, Russia, Canada
• Over 500 mill tons worth 1.15 bill USD
• Environmental challenges of hog farms
• International trade and increasing production

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Cassie Line EnviropigTM
Five months
Three months
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The Enviropig
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Cassie Line of Yorkshire EnviropigTM
7th Generation
6th Generation
6th Generation
2
1
1 Homozygote gilt SLI137 2 Homozygote gilt
SLI146 3 Hemizygote gilt SLI139 4
Hemizygote gilt SLI151
3
4
Hemizygous boar SLI153
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EnviropigTM Features
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Heart Healthy Pigs High Omega 3 Fatty Acid
PorkUniversities of Pittsburgh, Missouri
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Biotech Goats Milk will Help Worlds Children
Avoid Disease University of California Davis
andUniversity of Fortaleza and State University
of Ceara, Brazil

• Goal is to protect against the types of
  diarrheal diseases that each year claim the lives
  of more than 2 million children around the world.
• Scientists worldwide must demonstrate that the
  gene revolution may offer important tools for
  solving the problems of the very poor, much as
  the green revolution did during the 1960s.
• -Luiz Antonio Barreto de Castro,
• Brazils Ministry of Science and Technology

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Improving Milk Lysozyme GE Goats

• Goal is a herd within 2 years in Brazil, human
  trials in 3-5 years.
• Animals are normal- growth, reproduction,
  lactation
• No undesired expression of transgene
• Milk is normal, No unintended consequences in
  milk
• Anti-microbial activity of milk
• Shelf-life
• Impact of consumption

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Healthy Calves Resistant to BSE are Prion Free
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Healthy Dairy CattleResistant to Mastitis
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The Promise of New GE Traits in Animals

• Improved efficiency, rate of gain
• Enhancing meat composition
• Leaner meat
• Healthful lipids
• Enhancing milk
• Healthful lipids
• Casein ratios
• Lactose-free milk
• Human lactoferrin
• Bovine lactalbumin

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The Promise of New GE Traits in Animals

• Optimal animal welfare through disease resistance
• BSE KO of the prion protein
• FMD
• Avian influenza
• Mastitis
• Reduced environmental impact
• Growth rate efficiency
• Phosphorus use
• Improving hair and fibers
• Wool production

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Benefits of Genetic Engineering

• Enhancing food quality and safety
• Softer environmental footprint
• Enhanced animal health and welfare
• Advancing human health

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GE Animals Produce Antibodies To Fight Diseases
Formulate Vaccine
Genetically Modified Cell Bank
Clone Cow
Immunize Cow
Collect Plasma
Upstream Manufacturing
Bovine-derived Human Polyclonal Antibody
Purification of Product
Plasma
Downstream Manufacturing
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GE Animal Plasma Collection
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Xenotransplantation
/- GENETIC MODIFICATION (GT Knockout)
XENO-PRODUCTS
ORGANS
TISSUES
GM-Pig
CELLS
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Recent U. S. GovernmentRegulatory Progress

• 23 years ago, the Office of Science and
  Technology Policy Coordinated Framework (1986)
  provided a basis for regulatory review
• USDA regulates animal welfare reviewing public
  comments (Nov. 2008)
• FDA first regulatory guidance (Jan. 2009)
• FDA first approved product (Feb. 2009)

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ATryn is Recombinant Human Antithrombin

• Single Chain Complex Glycoprotein
• Difficult to Express in Cell Culture
• Found in Blood Plasma
• First Approval EMEA
• Second Approval US FDA
• NADA
• BLA
• Hereditary and Acquired Deficiencies

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Platform Technology
Transfer into recipient female
Purified Drug
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International Regulatory Approaches

• Codex Alimentarius approved a guideline for food
  safety assessment of GE animals on July 4, 2008
• FDA regulations are consistent
• There is support for international harmonization
  of safety assessment and regulations of
  genetically engineered food animals and their
  products.
• Other countries are developing regulations
  Argentina, Brazil, Canada, EC, Taiwan

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Other International Work

• Food and Agriculture Organization/World Health
  Organization food safety
• Organization for Economic Cooperation and
  Development (OECD) food safety, other
• World Organization for Animal Health (OIE) r DNA
  vaccines in future, may address GE impact on
  animal health
• Cartagena Protocol on Biosafety environmental
  impact

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What Do Consumers Think?
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IFIC 2008 Executive Summary
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• The majority of Americans (55 percent) have
  neutral impressions of animal biotechnology.
  Potential benefits of animal biotechnology have a
  positive impact on their impressions.
• 62 percent stated that safety and quality
  benefits associated with animal biotech have a
  positive impact on their impression.
• 55 percent were positively impressed by animal
  biotechs role in farm efficiency.
• 52 percent say that animal biotechs ability to
  lessen the environmental impact of animal waste
  has a positive impression on them
• Perceptions of genetic engineering and cloning
  continue to soften from previous years.
• Negative impressions of genetic engineering
  hold steady. As in 2007, more Americans hold
  neutral views today compared to 2005 and 2004 and
  fewer hold negative views.
• Compared to 2005 and before, favorable and
  neutral impressions of cloning have increased
  significantly.

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Impact of FDA Approval on Purchase of Products
from Cloned Animals
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2008 2007
2006 2005
05,
Likely
05,
Unlikely
05,
Q38. NEW Since OLD And if the U.S. Food and
Drug Administration (FDA) has determined that
meat, milk, and eggs from cloned animals
are/were safe, how likely are you/would you
be to buy them? Would you say...?
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Impact of FDA Approval on Purchase of Products
from Offspring of Cloned Animals
As with products from cloned animals directly,
nearly half of consumers are likely to buy
product from the offspring of cloned animals,
given the FDA determination that these foods are
safe. Previous years asked a hypothetical
question.
2008 2007 2006
Likely
Unlikely
Q39. NEW 2008 Since OLD And if the U.S.
Food and Drug Administration (FDA) has
determined that meat, milk, and eggs NEW from
the offspring of cloned animals are/were safe
OLD were safe from conventionally bred animals
whose parents were clones, but who are not clones
themselves, how likely are you/would you be to
buy them? Would you say...? Note Comparisons
to data collected prior to 2005 not feasible due
to changes in question wording.
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Impact of FDA Approval on Purchase of Products
from GE Animals
2008 2007 2006
2005 2004
Likely
Unlikely
Q35. If the U.S. Food and Drug Administration
(FDA) determined that meat, milk, and eggs from
animals enhanced through genetic engineering were
safe, how likely would you be to buy them?
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Transparency Communication and Education

• Domestic and international efforts
• Coalitions
• Communication plans media strategies
• Field trips
• Materials print and web-based
• Commissioned report on benefits of GE animals
• Food Dialogues
• BIO Guidance on Animal Biotechnology Stewardship
• Conference

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Future BIO Guidance on Animal Biotechnology
Stewardship

• The mission of BIOs APC Stewardship Initiative
  is to institute and promote guidelines for the
  development and use of GE animals, which promote
  animal welfare, enhance industry
  credibility, and complement current regulatory
  requirements
• Presentation at the 7th Transgenic Animal
  Research Conference August 17-21, 2009

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Future Livestock Biotech SummitThought Leaders
Progressing Animal Biotechnology for Global Needs

• Goal Solutions through agricultural animals in
  biomedical and agricultural research
• To increase visibility of the animal
  biotechnology industry, with focus on benefits as
  well as hurdles and challenges to advancement
  and,
• To educate on the requirements of the Animal
  Welfare Act including Institutional Animal Care
  and Use Committees (IACUC).
• Co-sponsors FASS interest from AAALAC, APLU,
  AVMA, FDA, IETS, NABR, NIH, USDA
• Late September, 2010, Sioux Falls, South Dakota

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Research Issue

• Applications whose primary aim is to improve the
  efficiency in the production of clones or
  transgenic animals through manipulation of the
  nucleus will no longer be accepted by the Animal
  Genome program.
• - AFRI Competitive Grants Program, FY 2009
  Request for Applications, USDA, CSREES

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Research Issue

• A key aspect of animal genomic research is using
  new technologies such as biotechnology for
  manipulation of gene expression in animals,
  including RNA interference and transgenesis.
• In the long-term, animal genomics efforts will
  lead to efficient and economical production of
  human pharmaceutical proteins in animals, and new
  technologies for manipulation of gene expression
  in animals (i.e., RNA interference, transgenesis,
  etc.).
• - USDA, 2007. Blueprint for USDA Efforts in
  Agricultural Animal Genomics 2008-2017)

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Research Funding

• BIO supports REE and NIFA
• We support increased public funding for food ag
  research
• BIO supports AFRI
• Support 300 million for FY 2010
• Reach fully authorized level of 700 million
• Many coalitions agree.
• BIO appreciates the change in the USDA Small
  Business Innovation rfp for FY 2010
• The exclusion on consideration of research on
  genetic engineering was removed.

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Research Funding

• We request that the exclusion of consideration of
  research proposals for cloning and genetic
  engineering be removed from the AFRI request for
  proposals beginning in FY 2010.
• All agree
• BIO member University of Guelph
• Academic scientists
• Dr. James Murray
• Dr. Matt Wheeler
• The Animal Agriculture Coalition

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University of Guelph

• Development of the Enviropig biotechnology would
  not have been possible without extensive
  financial support from Canadian Provincial and
  Federal research Funding agencies. - Dr. Cecil
  Forsberg, Professor Emeritus, and lead inventor
• The University of Guelph supports complete
  transparency related to publicly funded research
  in Canada, which has occurred with the Enviropig.
  Researchers at the University continually
  utilize public funding to support innovative
  research projects such as the Enviropig - Dr.
  David Hobson, Technology Transfer Manager

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• Final Thoughts on Tg Technology for Ag
• Cloning Risk Assessment
• -completed January 2008
• Guidance for Industry 187 Regulation of
• Genetically Engineered Animals Containing
• Heritable Recombinant DNA Constructs
• -completed January 2009
• 3) Funding for Transgenic and Cloning Research
• -very limited to non-existent Federal funds
• -technology development, innovation and training
• in the public sector is dying in this area in
  the USA

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Research Funding Solution

• Removing the exclusion will have a direct impact
  on academic and private research
• Slow down the exit from this area of research
  in academia
• Enhance graduate student and post-doctoral
  training
• Enhance collaborative research between academia
  and industry
• Will enhance the U.S. dominance in the area of
  genetic engineering and cloning of livestock
• Will provide scientific evaluation for food and
  health applications

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Challenges

• Availability of research funding and priority
  setting
• Adoption of cloning domestically and
  internationally
• Next GE product approval and international
  regulatory processes
• Consumer acceptance
• Anti-biotech activities
• Labeling
• Animal welfare
• Ethical issues
• Social, religious, other

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Opportunities

• New technologies from research will offer
  solutions to global problems
• Animal biotechnology will provide compelling
  benefits
• BIO works internationally
• BIO is conducting transparent communication and
  education of stakeholders and consumers, whose
  support we need

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Connecting to BIO, Our Industry

• BIO International Convention
• May 3-6, 2010, Chicago, IL
• GE Animal Resource Center- http//bio.org/foodag/
• Cloning- www.cloneinfo.org
• Dr. Barb Glenn, Phone [phone],
  bglenn_at_bio.org

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