Genetically engineered livestock – new technologies, new opportunities

Prof Bruce Whitelaw

New genetic engineering (GE) tools are exciting both the international animal breeding and biotech commercial sectors. Given the opportunities to enhance Indian agriculture and the pressing need this large country has for food security, it is very timely for both the Indian academic and commercial entrepreneurial communities to embrace this motivating prospect.

GE is a biotechnology tool involving manipulation of the genome of an organism. First applied in bacteria, GE mice followed quickly with initial success reported in 1974, followed by a rapid and huge uptake by the academic research community since. A decade later, the first GM livestock were produced in the US in 1985. Since then the gradual progress has deterred the wide scale application of the technology. Recent advances now change this entire sector. The genetic engineer, of which I am one, can alter the genome of animals in a precise manner; subtle genetic changes can be engineered which enhance the function of an animal.

Working in this field for nearly 30 years I have seen it first emerge then stutter its way forward. Initially, simply being able to add a gene (termed a transgene) to the genome was deemed a success. However, the tools available were crude. A transgene could be added but it would be integrated randomly within the genome. The result was an animal which may or may not show beneficial transgene activity. We could not control the outcome – we lacked precision. This is no longer the case.

The genome of an animal consists of about three billion bases (the bases are A, C, G, T). In this long ‘genomic text’ there are around about 20,000 genes. Genes encode proteins which make up the basis of animal life. We can now engineer in a predetermined manner exactly one base (the target site) in a specific gene – we can hit the ‘needle in the haystack’.

To engineer the animal genome we now use genome editing tools. These tools appear to offer the ideal technology for producing GE livestock; one that is both efficient and precise. They function as ‘molecular scissors’ cutting double stranded DNA precisely at a single, predetermined location in a genome. Thus specific allelic variation can be engineered, in essence capturing or copy what nature accomplishes through evolution – but on a much, much quicker timescale. Genome editor technology, beyond the desired allelic conversion event, leaves no ‘transgenic’ mark in the genome, and thus differs from the older technology. The impact this will have on regulatory processes and public opinion remains to be shown but has certainly enthuse the academic and interested the commercial sectors of our society. This emerging technology has the potential to be transformative in its impact if applied in the agricultural and biotechnology sectors.

During my current visit to India I will be presenting these scientific developments and the opportunities that spring from this new technical position at the International Animal Health and Welfare Conference in Bangalore and the 17th ADNAT Conference in Thiruvananthapuram. The former is organised by the Commonwealth Veterinary Association and provides a key event for promoting and supporting excellence in veterinary education at an international level. At this event I will expound how this technology can be appropriately and successfully applied to agriculture, highlighting opportunities to increase animal welfare. At the latter Conference on Genomics in Personalised Medicine and Public Health, I will focus on biomedical applications. I also have the opportunity to address a wider audience at my public lecture hosted by the Karnataka Veterinary Council in association with the Royal (Dick) School of Veterinary Studies of the University of Edinburgh. I am very much looking forward to present the exciting prospect of using these new genetic tools to enhance India agriculture and provide commercial opportunities to the growing Indian bioscience community. In this regard, the progressing thinking by the Department of Biotechnology to establish a National Institute of Animal Biotechnology in Hyderabad provides a strong platform for the fusion of academic and commercial interests in this field.

To demonstrate the power of this new technology we have embarked on key projects at The Roslin Institute of the University of Edinburgh, many of which could be easily and quickly developed further in India. Our initial projects aim to enhance the resilience of animals to infectious disease with the dual benefit of positively impacting on both productivity and animal welfare in agriculture. Important target diseases include those most severely affecting animal production, for example Foot and Mouth Disease (FMD), and zoonotic threats such as influenza.

Infectious disease is the biggest threat to food security in the 21st century. As livestock production intensifies the industry becomes more vulnerable to devastating disease outbreaks potentially affecting millions of animals (recent examples in the UK being Classical Swine Fever, and Foot and Mouth Disease). In addition to significant primary production losses to individual farmers and disruption of supply chains, it can also result in collateral national losses due to export restrictions. Veterinary measures such as vaccines or traditional genetic selection are unlikely to provide complete protection from the threat of epidemic disease, whereas more radical solutions do have such potential. The recent breakthroughs in genome engineering technology offer the possibility of developing animals with complete resistance to specific disease pathogens by simultaneously interfering with the biology of the disease agent at multiple points, reducing the possibility that the pathogens can mutate to become infectious to the resistant animals. In addition to enhanced productivity there will be obvious animal welfare benefits of this approach.

FMD is an OIE-listed disease. It is highly contagious and is perhaps the most feared disease amongst farmers of cloven-footed animals. In South Asia FMD is a priority disease, with an estimated 600 million susceptible farm animals. In Indian livestock, particularly cattle, buffaloes and small ruminants have a great importance to food security, nutrition and livelihoods, the annual loss due to FMD has been estimated at $800 million. The devastation that this disease can impact on small rural farming communities goes well beyond monetary concerns. Even in countries designated free of FMD, outbreaks can have significant economic damage and social disruption as seen recently in the UK.

The main approach to combating viral infection is through the use of vaccines and although vaccination strategies can have a significant impact on the prevalence of FMDV, they are limited in that there is no cross-protection between the seven serotypes that exist worldwide. Moreover, since FMDV exists in wild-animal reservoirs around the globe, re-introduction of the disease into domesticated livestock poses an on-going problem. Therefore alternative approaches to combat FMDV should be evaluated to complement on-going strategies to combat this disease – and we are proposing that GE technology could have a significant role in producing animals that are better able to combat this dreadful disease.

We are also evaluating genetic engineering solutions to combat influenza in agricultural animals. Influenza also on OIE-listed disease, spreads around the world in seasonal outbreaks causing up to half a million human deaths per year. Although birds are the main animal reservoir from which arguably all new strains have their inception, influenza virus infects many animal species and transfer of viral strains between species occurs. This includes humans and thus this is a zoonotoic disease. Vaccines are available but differ in effect between virus strains. A genetic approach would offer a long-term solution to controlling this disease.

The recent development of genome editor technology has reawakened commercial interest in the use of GE livestock in animal breeding for agriculture and has the potential to re-shape the debate in this area. Genome editor technology, beyond the desired allelic conversion event, leaves no ‘transgenic’ mark in the genome. Opportunities for both the academic and commercial communities abound. I look forward to exploring the development of this biotechnology in India through colleagues and friends.