Animal Health and Welfare Alison Van Eenennaam, Ph.D. Cooperative Extension Specialist Animal Biotechnology and Genomics Department of Animal Science University of California, Davis, USA

[email protected] @BioBeef Blog: http://biobeef.faculty.ucdavis.edu

http://animalscience.ucdavis.edu/animalbiotech

Van Eenennaam BIO 9/21/2016 Animal Genomics and Biotechnology Education https://youtu.be/C0MBl0BANHg Animal biotech is often associated with only one application

BIO 9/21/2016 Animal Biotechnology and Genomics Education Sustainability implications of land-based AquAdvantage aquaculture

√ More efficient: Less feed to produce a serving of fish √ Less disease spread to wild populations √ Decreased use of antibiotics

BIO 9/21/2016 Animal Biotechnology and Genomics Education

Genetically engineered Glofish Pigs as organ donors - xenotransplantation

• http://www.glofish.com BIO 9/21/2016 Animal Genomics and Biotechnology Education Genetic improvement (permanent, cumulative) as a solution to animal disease rather than chemicals

BIO 9/21/2016 The influenza pandemic of 1918 killed between 20-40 million people - more than died in WWI

BIO 9/21/2016 Animal Genomics and Biotechnology Education GE Chickens That Don't Transmit Bird Flu Breakthrough could prevent future bird flu epidemics

Science 331:223-226. 2011 www.roslin.ed.ac.uk/public-interest/gm-chickens BIO 9/21/2016 Animal Genomics and Biotechnology Education TRYPANOSOMIASIS (African sleeping sickness) in SUB-SAFARAN AFRICA

• Several thousand people die of African sleeping sickness and 3 million cattle deaths annually • 35 million doses/year of Trypanocidal drugs • 13 countries have resistance to these drugs • 90% of the crops grown in sub- Saharan Africa are produced without animal power, which costs the continent more than $4 billion in losses every year

http://www.ilri.org/breadtrypanosome

BIO 9/21/2016 Slides: Jayne Raper; CUNY Animal Genomics and Biotechnology Education Baboons are resistant to all African trypsosomes

• Resistance arose 9 million years ago

• Baboon “ApoL-1” gene gives GE mice complete X protection from all African trypanosomes Thomson et al (2009) PNAS 17: 19509-14 BIO 9/21/2016 Slides: Jayne Raper; CUNY Animal Genomics and Biotechnology Education

$2 million grant from the Bill & Melinda Gates Foundation and the US National Science Foundation to develop trypanosomiasis-resistant ApoL-1 GE cattle.

• Trypanosomiasis is a disease caused by blood parasites of the genus Trypanosoma and transmitted in Africa by tsetse flies (Glossina spp). More than 30 tsetse fly species and subspecies infest an area of 8.7 million

http://www.genomics.liv.ac.uk/tryps/Key_Papers/PuttingSleepingSicknessToBed.pdf BIO 9/21/2016 Animal Genomics and Biotechnology Education Holtkamp et al. 2015. Gene- edited pigs are protected from porcine reproductive and respiratory syndrome virus (PRRSV). Nature Biotechnology

http://dx.doi.org/10.1038/nbt.3434

BIO 9/21/2016 Animal Biotechnology and Genomics Education British Foot & Mouth Outbreak

www.visitcumbria.com

http://news.bbc.co.uk/ BIO 9/21/2016 Animal Biotechnology and Genomics Education Foot & Mouth Disease in UK • 6 to 10 million animals slaughtered from 10,000 farms • $ 3.5 to $ 6 billion lost, Numerous producer suicides

www.eu2001.se BIO 9/21/2016 Animal Biotechnology and Genomics Education There are disease-resistant animal applications with compelling animal welfare and human health benefits

Van Eenennaam, A.L. and A.E. Young. 2015. Animal agriculture and the importance of agnostic governance of biotechnology. Agriculture and Food Security 4:21 BIO 9/21/2016 Animal Biotechnology and Genomics Education Gene Edited Polled Calves Naturally-occurring bovine allele at polled locus

Carlson DF, Lancto CA, Zang B, Kim E-S, Walton M, et al. 2016. Production of hornless dairy cattle from genome-edited cell lines. Nat Biotech 34: 479-81

BIO 9/21/2016 AnimalAnimal GenomicsBiotechnology and andBiotechnology Genomics EducationEducation https://www.youtube.com/watch?v=-Qks_LMmodw

Animal Biotechnology and Genomics Education Animal biotechnology applications align with many sustainability goals including improved animal health and welfare, decreased use of antibiotics and chemicals & reduced environmental footprint

• Naturally polled Holsteins • Disease resistant animals • Sex selection for ♀ in dairy and egg industries

Animal Biotechnology and Genomics Education Breeding Method: Selective Breeding Genomic Selection Species Mutagenesis (ENU) Gene Knockout (ES) Genetic engineering Sterile insect technique Cloning Gene Editing

Research Biomedical Pharma Pets Pest Control Agriculture TseTse fly – Millions of Products products GloFish sleeping sickness AquAdvantage Salmon – Rabbit - Mice/Laboratory Cattle – polyclonal Micropigs Mosquitoes – fast growth Ruconest Rodents/Zebrafish human antibodies zika/malaria Polled Holsteins Goat – ATryn, Pigs – resistance Disease resistance spider silk; Moths – Improved product quality Xenotransplantation; Chickens – agricultural pest Decrease environmental Blastocyst Kanuma control footprint complementation Cows – Single gender offspring polyclonal antibodies

BIO 9/21/2016 Animal Genomics and Biotechnology Education Merging values and technology

All agricultural and medical production practices impact the environment and can have adverse effects on biosafety, and the conservation and sustainable use of biological diversity.

Regulatory frameworks should formally evaluate the reasonable and unique risks associated with the use of biotech animals (and other biotechnologies) in agricultural systems, and weigh them against those associated with existing conventional systems, and those of inaction (i.e. postponing a regulatory decision). Perhaps more importantly these risks have to be weighed against the benefits. This would represent a shift away from an uneven risk-assessment process that emphasizes ever diminishing marginal hazards, to one that includes a risk:benefit analysis to more objectively evaluate and communicate the likely impacts of approving a new biotech animal.

BIO 9/21/2016 Animal Biotechnology and Genomics Education

The first product from a transgenic farm animal to become a registered drug was Antithrombin III from rEVO Biologics , USA, produced in the mammary gland of GE goats for heparin resistant patients to prevent blood clots

February 2009, First GE Animal Product http://revobiologics.com BIO 9/21/2016 Animal Genomics and Biotechnology Education In 2014 USA approved a drug produced in mammary glands of GE rabbits for patients suffering from HAE which is a disorder characterized by recurrent episodes of severe swelling (angioedema)

July 2014, Second GE Animal Product http://www.salix.com BIO 9/21/2016 Animal Genomics and Biotechnology Education In 2015 USA approved a drug Kanuma produced in eggs of GE chickens for patients suffering from lysosomal acid lipase deficiency (LAL-D) which is a disorder characterized by multi-organ damage and premature death December 2015, Third GE Animal Product http://alexion.com/ BIO 9/21/2016 Animal Genomics and Biotechnology Education GE mosquitoes for zika, dengue control

• 2015 Florida Keys project http://www.oxitec.com/health/florida-keys-project

BIO 9/21/2016 Animal Genomics and Biotechnology Education Nature Biotechnology 20:889-894. 2002

Transchromosomal cattle carry a human artificial chromosome harboring the entire sequence of the human major histocompatability complex . These animals were cloned from bovine fibroblasts after transfection with the http://Sabbiotherapeutics.com additional chromosome. BIO 9/21/2016 Animal Genomics and Biotechnology Education Plasmapheresis to extract polyclonal antibodies from the blood of cloned, transchromosomic, knockout cattle carrying human immunoglobulin

BIO 9/21/2016