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Introduction

Over the past century, worldwide consumption of food-animal products such as meat, milk, and eggs has steadily grown due to increases in global population and per capita income that fuel demand for high-quality, protein-rich diets. The U.S. Department of Agriculture Economic Research Service predicts that as the world population grows to a projected 9.7 billion people in 2050, global agricultural production will have to increase almost 50 percent from 2011 levels (Sands et al., 2023). Faced with constraints in land, water, and other inputs that limit agricultural expansion, plus increasing levels of socioeconomic status globally, food-animal producers are trying to meet the demand for food-animal products by improving the productivity of animals using scientific insights into the biological characteristics (traits) associated with animal productivity and health, knowledge about the genetic basis of beneficial traits and variations, and novel tools to assist in developing food-animal populations that carry those traits.

Food-animal breeders have traditionally used selective breeding to maximize the intrinsic productivity and health of food animals. This is accomplished by the selection of animals that display beneficial traits to serve as breeding partners in the expectation that their offspring will exhibit a profile (phenotype) of traits that reflects or exceeds the beneficial attributes transmitted by their parents. While straightforward, a positive outcome of this approach is not guaranteed. The offspring produced will typically exhibit varying phenotypes relative to the parent animals and each other and may present some but not all traits exhibited by the parents. In recent decades, selective breeding has been strengthened using statistical methods to better assess the potential that an individual animal will produce offspring with the desired traits. Programs of selective breeding have led to considerable gains in livestock productivity in many species, including chickens (Havenstein et al., 2003; Zuidhof et al., 2014), dairy cattle (Capper et al., 2009; Capper and Cady, 2019), and fishes (Gjedrem, 2000; Gjedrem and Baranski, 2010).

The recognition that the characteristics of most traits are shaped by multiple genes has led researchers to identify sets of genetic markers within the genome of an animal species that denote “quantitative trait loci,” that is, patterns of genes associated with trait variations. This knowledge supports the practice of marker-assisted genomic selection (Meuwissen et al., 2001), in which a DNA sample taken from an animal is sequenced to indicate its genetic makeup (genotype) relevant to a trait of interest to evaluate the animal’s potential desirability as a breeding candidate. Marker-assisted breeding has been particularly successful for dairy cattle, where multiple generations of phenotypic data and genomic data are available (Weigel, 2017; Weigel et al., 2017).

Although these tools help inform the selection of animals with desired traits for breeding, the process of obtaining the right mix of traits and incorporating those genetic variations and traits into animal herds and bird flocks

takes time, relying on many rounds of breeding to obtain the desired phenotype that is predictably spread through offspring. Recent advances in the fields of genomics and biotechnology have generated powerful new techniques for faster genetic improvement of food animals using heritable genetic modification (HGM) techniques that make changes to an animal’s DNA. The potential contributions of animal biotechnology to genetic improvement of food animals are substantial, distinct from, and complementary to those of conventional selective breeding. Two examples described briefly here and in greater detail in the body of the report include classical gene transfer and genome editing.

Gene transfer involves human-mediated insertion of genetic material into a cell with the intent that it becomes integrated into host DNA, is expressed, and alters the host phenotype in a purposeful manner. For example, the growth hormone (GH) gene can be microinjected into a newly fertilized embryo and become randomly integrated into the genome of the newly developing organism. After implantation and birth, the animal’s genome overexpresses growth hormone, which creates rapid growth, and because the gene is integrated into the genome, it is heritable by future generations. The AquAdvantage GH transgenic Atlantic salmon that was approved by the U.S. Food and Drug Administration (FDA) in 2015 is one example of the application of technology that is commercially available (FDA-CVM, 2015).

Genome editing involves use of site-directed nuclease enzymes to make a change to an organism’s DNA, allowing genetic material to be added, removed, or altered at targeted locations in the genome. This approach has been applied, for example, to knock out part of the CD163 gene in pigs, eliminating part of a cellular receptor that the porcine respiratory and reproductive syndrome virus uses to gain entry into the cell and cause porcine respiratory and reproductive syndrome (Wells et al., 2017).

Although the use of HGM techniques has great potential for the genetic improvement of agricultural animals for a wide array of traits from productivity and disease resistance to animal welfare benefits, it has also raised animal safety, food safety, and other concerns (NRC, 2002). The term “concern” as used in this report was defined by the National Research Council as “an uneasy state of blended interest, uncertainty, and apprehension” (NRC, 2002). Because HGM techniques are relatively novel, FDA, which regulates the use of biotechnology in food animals, has been cautious and methodical in exploring potentially unintended consequences of the technique that might present a hazard to human health or animal welfare. At this time, only two food animals modified by HGM techniques have been approved or authorized by FDA for human consumption.¹

STUDY ORIGIN

In the 2023 Appropriations Bill for the U.S. Department of Health and Humans Services, Congress directed the National Institutes of Health (NIH) to request the National Academies of Sciences, Engineering, and Medicine to conduct a consensus study to “identify the biological basis of health risks relevant to the regulation of heritable genetic information in food animals. This includes the identification of genetic and other molecular mechanisms that could present risks to human and animal health and well-being based on heritable genetic information (natural, induced, intended, or designed) in food-animal species.”² In response to the subsequent request from NIH, the National Academies established the Committee on Heritable Genetic Modification in Food Animals to carry out the consensus study. The charge to the committee is provided in Box S-1.

The frameworks of risk analysis and risk management, as detailed in the National Research Council “Red Book” (NRC, 1983) are relevant to the committee’s approach to its task. The critical terms used in risk analysis are hazard, harm, and exposure. Risk is the probability of a defined harm becoming realized within a defined population. Although risk defined in this way can prove rather nebulous, it can be broken down into terms that are manageable. Risk can be recast as the product of two probabilities: (1) the probability of a defined harm being realized given exposure to the hazard, and (2) the probability of exposure to the hazard. Essentially, risk analysis

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¹ See https://www.fda.gov/animal-veterinary/biotechnology-products-cvm-animals-and-animal-food/intentional-genomic-alterations-igas-animals.

² House Report 117-403, Departments of Labor, Health and Human Services, and Education, and Related Agencies Appropriations Act, 2023.

aims to identify all possible hazards and all possible harms that can result from exposure to those hazards. Risk management explores mechanisms that can reduce or eliminate exposure to a defined hazard. These concepts were first applied to animal biotechnology by the National Research Council (NRC, 2002) and were further explored by the committee as it considered what is known about the potential hazards of HGM techniques and how they do or do not translate into potential risks to human health and animal welfare.

BIOTECHNOLOGY TERMINOLOGY

For clarity, terms that have been used in discussions of animal biotechnology in this report are defined in Box 1-1. These terms differ in nuance and utilization among regulatory agencies, countries, and international groups of countries but they are, to varying degrees, equivalent.

REFERENCES

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