(Note: Since the 10th Biennial Transgenic Animal Research Conference (TARC X) conference was held in August 2015, the AquAdvantage salmon was technically approved by the FDA in November 2015, although currently it can still not be sold in the United States as explained here.)
The first transgenic animal research conference (TARC I) was held in 1997 and the proceedings were summarized in a book optimistically titled, “Transgenic Animals in Agriculture”. The book contains some interesting quotes, including one attributed to Dr. Robert Wall, USDA-ARS in Beltsville, Maryland, who quipped, “the field of transgenic large animals is one of the few fields where there are more review papers than data papers.”
It is perhaps a useful exercise at this TARC X conference to go back to some of those original papers and see what progress we have made over the past 18 years. At the time it was posited that there were three major limitations to wide-scale application of transgenic technology to improve farm animals: 1) lack of knowledge concerning the genetic basis of factors limiting production traits, 2) identification of tissue and developmentally-specific regulatory sequences for use in developing gene constructs, expression vectors and in gene targeting, and 3) establishment of novel methods to increase the efficiency of transgenic animal production. Considerable progress has been made in all three of these areas in the past 2 decades.
Despite the hopeful projection offered by Dr. George Seidel of the Animal Reproduction and Biotechnology Laboratory at Colorado State University, “At this point in evolution, human society places great emphasis on applications of science and technology. Since use of transgenic technology in farm animals, almost by definition, is an application, this will be viewed favorably by both public and private funding sources”, limited progress has been made in the commercialization of transgenic animals.
Pharmaceutical proteins ATryn® and Ruconest®, produced in transgenic goats and rabbits, respectively, have been approved in both the European Union and the United States. Several varieties of fluorescent transgenic aquarium fish are being marketed throughout the United States as GloFish®, and open field trials of genetically engineered male insects produced by Oxitec have been carried out in several countries to reduce the population numbers for disease-spreading pests. However, no transgenic animal has yet been approved for food purposes anywhere in the world, despite an ongoing long-term attempt by AquaBounty to obtain a U.S. regulatory decision for their fast-growing Atlantic salmon.
The lack of progress on agricultural applications can be attributed to a scarcity of both public and private funding sources, and the absence of a clear path to market. Starting in the mid-2000s, the annual USDA request for grant applications included the following ominous text, “Applications whose primary aim is to improve the efficiency in the production of clones or transgenic animals through manipulation of the nucleus will no longer be accepted by the Animal Genome program”. This directive continued for almost a decade. There has likewise been little private sector interest in taking transgenic food animals, such as the phytase-expressing Enviropig™, through an expensive and unpredictable regulatory process. In the absence of any approved food animal applications, there has been little support or market pull for transgenic animals from the livestock breeding sector.
As a scientific community, we have continued to make progress in transgenic animal research methods, funded mostly by granting sources interested in the biomedical application of transgenic animals, and also the USDA Biotechnology Risk Assessment Grant (BRAG) program. This program has funded research to test some nontraditional hypotheses to provide rigorous scientific data for risk assessments.
Dr. Matthew Wheeler, University of Illinois, answered the question of whether transgenes can be transferred directly from transgenic pigs to control swine by physical association or contact, by mating, or from a transgenic dam to her non-transgenic offspring during lactation. Spoiler alert # 1: The data showed no transfer.
In another project, Dr. Elizabeth Maga, University of California, Davis (UCD) answered the question of whether transgenic goats expressing lysozyme in their milk behave differently to control goats. Spoiler alert # 2: The data showed no difference.
In the first chapter of “Transgenic Animals in Agriculture”, Dr. Jim Murray, UCD wrote, “Our role as scientists, consumers, and regulators is, in part, to decide at what level or stages and to what degree the development of agriculturally important transgenic animals must be monitored and regulated to ensure consumer safety and animal well-being, and address societal concerns. A further corollary to this responsibility is to ensure that the consuming public understands the processes to the extent that they can accept government approval of such animals in the food chain.”
I would argue that less progress has been made in this area. In the chapter penned by Dr. Joy Mench, UCD, which focused on the ethics and animal welfare of transgenic farm animals, she warned, “In the past scientists have tended to isolate themselves from these debates. This posture needs to change. Scientists need to become full and fully informed participants in the debate about the ethical effects of the technologies that their work is instrumental in developing. Otherwise, consumer confidence in science and scientists may well be lost.”
Is it finally time for the transgenic animal scientific community to take these suggestions to heart and address both the regulatory impasse and the consumer concerns head on? The current recombinant DNA (rDNA) process-based trigger for regulatory evaluation of transgenic animals is disincentivizing the development of beneficial transgenic animal applications. As a community, we need to push for sensible regulatory reform.
Regulatory effort should be proportional to the risks posed by the product. Required regulatory studies should be hypothesis-driven based upon the novel attributes of new varieties in relation to known risks associated with existing varieties, and not on the breeding method used to develop the new variety.
The closing speaker at the 1997 conference, Dr. George Seidel suggested, “One mistake that animal scientists are rightly accused of making is to emphasize production traits when low production is not a problem. More attention needs to be paid to non-production traits such as animal welfare, animal health, consumer acceptance, and so on.” I contend that we now have applications that address these non-production traits and it is time for scientists to more effectively communicate the compelling narratives associated with the potential benefits of these technologies.
It would be ironic if, as was portended by Joy Mench at TARC I in 1997, “genetic engineering turned out to be the fastest and best solution for some of the welfare problems that we have created using traditional breeding methods like leg problems in broilers.”
Scientific and technological advances in disparate animal breeding research communities over the past two decades are now undergoing a form of scientific convergent evolution. The thousands of SNP markers discovered through livestock sequencing projects, the information obtained from numerous genome wide association studies, the discovery of causative SNP (QTNs), the development of genomic selection statistical methodology to include molecular data in genetic merit estimates, genome editing techniques, and transgenic technologies are all useful individually. But collectively, they offer a powerful approach to accelerate real genetic change in our food animal species to the advantage of food security and agricultural sustainability globally.