“Bio-Engineering” in LivestockHow do these “tools” fit into modern livestock

production?

Chad J. Mueller, PhD

Dept. of Animal Sciences

+ =

Is this “Pandora’s Box”, and why did we open it?

• Cheap food = lower market prices!!– Not expenses!!

• Growing populations = less tillable acres + greater regulations

• Less producers & higher labor costs

What are these “Bio-engineering” tools?

• Metabolic modifiers

• Transgenics

• Cloning

“Bio-engineering” tool:Metabolic Modifiers

Metabolic modifiers

• Compounds that modify animal metabolism in specific and directed ways.– Improve gain and lactation efficiencies, reduce

waste output

– Two main classes• Somatotropins (STs)-adrenergic agonists

Metabolic modifiers: Somatotropins

• Use of recombinant DNA technologies– Specie-specific proteins (pituitary gland)

– Dairy (bovine ST) & swine (porcine ST) industries

• bST:– Commercial sales began in 1994

• Posilac™• Used in approx. ½ U.S. dairy herds• Used in 19 countries

milk production (8 – 10 lb./hd/d), lactation efficiency (milk / feed)

Metabolic modifiers: Somatotropins

• pST:– Improved nutrient use for lean tissue production

• Less fat!• Improved carcass value

– Less dietary protein required• Reduced N waste per unit of feed (pollution)

– Currently being tested by FDA• Commercial use by 14 countries (Etherton et al., 2003)

Metabolic modifiers: -adrenergic agonists

• Known as:– Phenethanolamines

– Repartitioning agents

• Similar in structure to catacholamines– Dopamine, norepinephrine, epinephrine

– Use same cell receptors ( or -receptors)

• Stimulate protein anabolism, reduce protein turnover and lipogenesis lean tissue, % carcass fat

Metabolic modifiers: -adrenergic agonists

• U.S. = Ractopamine– 2 commercial products

• Paylean 9™ for swine• Optaflexx 45™ for beef cattle

“Bio-engineering” tool:Transgenics

Transgenics

Two common methods:• Injection of DNA into

pronucleus of fertilized ovum

• Targeted insertion of DNA through embryonic stem cells

Transgenic animals carry and express genetic information not normally found in that host or species

Transgenics

• 1981: First transgenic mouse– Insertion of hGH into a mouse (Singleton, 1999)

– Production of monoclonal antibodies & anti-inflammatory agents

Transgenics

• Why use transgenics?– Study gene function and regulation

• Genome mapping

– Model development and progression of human diseases

• Cystic fibrosis• Multiple sclerosis

– Xenotransplantation• Disruption of Gal1-3Gal enzyme• Disrupt human viral diseases

– Hepatitis & liver transplants

CAST, 2003

Transgenics

• Benefits of transgenics in animal production?– Phytase enzyme in swine / poultry

– Improved gain efficiency and protein production• Super-salmon

– Antifreeze protein in flounder + Chinook salmon

– Reduced-lactose milk

– Human therapeutic proteins• Antithrombin III, lactoferrin, monoclonal &

polyclonal antibodies, serum albumin

PEW Initiative, 2005FDA, 2005

Transgenics

• Functional genomics must be understood– Single-gene traits vs multiple-gene traits

• Is there a marketable impact?– Economically & sociably

• “Input” traits vs “Output” traits

Bremel et al., 2001

“Bio-engineering” tool:Cloning

Cloning

• The production of genetically-identical animals by nuclear transfer from somatic cells to unfertilized eggs.

Tian et al., 2003. (Reprod. Biol. and Endo.)

Cloning

• Cloning through the ages:– 1952: Cloning via nuclear transfer (frog)

– 1989-1990: First mammals cloned

– 1995: First cloning via cultured mammalian cells

– 1997: First cloning via adult cells – DOLLY• First cloning via transgenic adult cells – POLLY

– 1998 – 2000: Cloning of cattle, pigs, mice, goats and monkeys using adult cells

– 2001: First reported cloned human embryo

– 2002: First cloned pet

Cloning

• Applications:– Reproduce superior traits

• Growth, milk production, etc.• Especially in conjunction with transgenics

– Facilitate “pharm” animal production• Human therapeutic proteins• Xenotransplantation

– Bio-terrorism defenses production of antibodies to botulinum toxin in milk

Cloning

• Applications:– Recover “lost” or “endangered” species

• Pets?

Cloning

• Very expensive

• Technology needs continued refinement– Nuclear transfer is successful <1% of the time

• High rates of pregnancy loss and neonatal death

• Developmental abnormalities– Incomplete reprogramming of genome

– Incomplete epigenetic reprogramming

“Bio-engineering” tools:Ethical Considerations

Benefits vs Risks

Ethical Considerations

• “When faced with serious illness, most people are willing to take risks to combat a disease. Food is different…since it is so basic, both physically and emotionally. It's not surprising that consumers are extremely averse to any food-related risk, especially if the risk is perceived as imposed by someone else, beyond individual control and without any countervailing benefit. Consumers…are concerned mostly about such potential health problems as allergic reactions and antibiotic resistance.”

Carol Tucker Foreman, Director of the Food Policy Institute at the Consumer Federation of America (CFA) in Washington, D.C.

• Metabolic modifiers:– Health risks to humans?

• Effect on human growth?• Allergies?• Should food products be labeled?

– Animal welfare• Developmental and health issues

– Mastitis, heart palpitations, conception rates, inflammation of injection sites (bST), arthritis, lameness

Ethical Considerations

• Transgenic animals:– Health risks to humans?

• Effect on human growth?• Allergies?• FDA says “NO” to consumption

– Animal welfare• Developmental problems due to introduced genes

– Arthritis, gastric ulcers, high mortality rates, degenerative joint disease

• Issue of animals with only partial gene incorporation?

Ethical Considerations

• Cloned animals:– Health risks to humans?

• FDA says “OK” to consumption

– Animal welfare• Poor survivability rates, developmental problems,

behavioral abnormalties• Shortened life spans, health problems

Ethical Considerations

Ethical Considerations

• Additional clone and transgenic animal issues:– “Accidental” incorporation of animals to wild

populations

– Limited gene pool?

– Impact on the use of certain resources

– What information do we lose by “speeding up” the generation interval?

– Morally…are we “playing God”?

Legislative regulation

• Food and Drug Administration (FDA)– Center for Veterinary Medicine

• 2003 – 2004 legislative session– 16 bills on transgenic fish

– 13 bills on transgenic plants and animals for “pharma” applications

• Public is worried about who is in control– Private enterprises vs government

Questions to Ponder!!

• Should farm animals be bio-engineered for food production?

• Cloned animals: What traits are superior, and should we value variation?

• Who should be “in charge” of this technology, or ultimately who is responsible for this technology (and it’s consequences)?

• Should the public consider “food production” and “Pharm production” as separate issues?