Genetic modification of food animals

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Highlights

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    Genetic improvement decreases the environmental footprint of animal-source protein.

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    New breeding methods enable precise intraspecies and interspecies allele substitutions.

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    Disease resistance and welfare traits have been targeted for genetic improvement.

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    The regulatory status of animals produced using gene editing techniques is unclear.

Animal breeders have used a variety of methods in selective breeding programs to genetically improve food animal species. Recently this has included the use of both genetic engineering and genome editing, particularly for targeting improvement in traits for which there is no within-species or within-breed genetic variation. Both intraspecies and interspecies allele substitutions and gene knock-ins have been accomplished with genome editing tools, targeting a number of important traits. The regulatory status of such animals is unclear as the definition of a regulated article is not consistent among different regulatory agencies and organizations. In the absence of a harmonized global regulatory approach to the genetic improvement of animals, it will be difficult for breeders to effectively achieve sustainable breeding objectives.

Introduction

Animal breeders have been directing livestock evolution since animals were first domesticated. Initially, the tools available to breeders were simply observations on what was perceived to be the desired appearance and the selective mating of chosen parents. One only needs to look at the differences between a Chihuahua and a Great Dane, relative to their wild ancestor the wolf, to appreciate that conventional selection is a powerful force for genetic change. Over time, the tools and methods used to make genetic improvement have advanced, and this has accelerated the rate of genetic change. Subjective observations were replaced by objective measurements, and sophisticated statistical methods were implemented to isolate heritable genetic effects from environmental influences [1]. The rate of genetic improvement was further accelerated by combining genetic selection methods with advanced reproductive technologies (ART) such as artificial insemination (AI) and embryo transfer (ET).

The impact of selective breeding programs on the footprint of agriculture and food production is difficult to overstate. It has been estimated that historic genetic improvement in selected traits (e.g. milk/meat output, growth efficiency) has resulted in a 1% per year reduction in greenhouse gas (GHG) emissions per unit food produced (e.g., a tonne of beef/sheep meat) [2]. Capper et al. [3] compared the environmental footprint of US dairy production between 1944 and 2007 and reported that although the carbon footprint per individual cow had increased over time, the carbon footprint per unit of milk was 63% lower in 2007 than it was in 1944. Perhaps this point is best illustrated by calculating that, sans genetic improvement, we would need in excess of 30 million dairy cows in the United States to produce the amount of milk that 9 million cows were able to produce in 2014. Genetic improvement is undoubtedly one of the most powerful drivers of agricultural sustainability.

Given this history and the fact that conventional, or ‘artificial’, selection is largely uncontroversial, it might be expected that innovations in breeding methods would be mostly undisputed as self-evident approaches to help meet the projected increase in global animal protein demand. However, this is clearly not the case given the decades-old global debate [4] over the use of one particular breeding method, genetic engineering. Plants and animals that are destined for food and which have been genetically modified using this particular breeding method, although interestingly not those modified for medical purposes using exactly the same techniques, generate absolute moral opposition [5] and have been at the epicenter of a controversial and rancorous scientific debate. This review will discuss recent developments in the use of modern biotechnologies in food animal breeding programs.

Section snippets

Genetic engineering

One definition of genetic engineering (GE) is a process in which recombinant DNA (rDNA) technology is used to introduce desirable traits into an organism. The real power of this technology is in enabling breeders to access genetic variation that is not otherwise normally present in the target species, especially for traits such as disease resistance. Genetically engineered animals were first produced in the late 1970s, and the first GE livestock were produced in 1985 [6]. Thirty years later, GE

Genome editing methods

Genome or gene editing refers to the use of site-directed nucleases (SDN) to precisely introduce a double stranded break (DSB) at a predetermined location in the genome. The cell can repair that DSB break in one of two ways — homologous recombination (HR) using a nucleic acid template that includes the sequences homologous to either side of the double-strand break, or nonhomologous end joining (NHEJ). The outcomes of these repair processes result in precision gene edits or random mutations,

How might gene editing be used in animal breeding?

In the last 5 years, SDNs (zinc finger nucleases (ZFNs) transcription activator-like effector nucleases (TALENs), and clustered regulatory interspersed short palindromic repeats (CRISPRs) associated system) have been used to mediate the generation of 300 gene edited pigs, cattle, sheep and goats [18••]. Several recent reviews describe the potential to use these tools in food animals for agricultural purposes [8, 9, 18••, 19, 20, 21], and include detailed descriptions of their mechanics and

How might gene editing intersect with conventional breeding?

To become an important driver of genetic change, gene editing methods must seamlessly integrate with conventional animal breeding programs. That means that they must reliably function to germline-edit animals that are selected to be the next generation of parents. Edits can be introduced through gene editing of somatic cells followed by somatic cell nuclear transfer (SCNT) cloning, or injection of the gene editing reagents into the cytoplasm of single cell zygotes of the next generation.

To

Will gene editing be regulated?

Many agencies are involved with the regulation and governance of genetically engineered animals including the United States Food and Drug Administration (FDA), the European Medicine Agency (EMA), the European Food Safety Authority (EFSA), and the Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO). The definition of a ‘genetically engineered’ animal differs among these different agencies.

The Codex Alimentarius (Codex), or ‘Food Code’, was established by

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

This work was supported by Biotechnology Risk Assessment Grant Program Competitive Grant no. 2015-33522-24106 and Agriculture and Food Research Initiative Competitive Grant no. 2015-67015-23316 from the National Institute of Food and Agriculture/U.S. Department of Agriculture. Special thanks to Amy E. Young for assistance in preparation of the figures.

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