standard Animal and Insect Transgenics – Parallels

James Murray and Elizabeth Maga recently recounted briefly the development and evolution of animal transgenic technologies in a recent issue of Transgenic Research and the similarities and differences between the development and evolution of insect transgenic technologies, which were ongoing in parallel but largely independently over the same 30-year period, are interesting – particularly their critique of the current regulatory environment that might best be summarized as muddled and a drag on ongoing development efforts.

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Mouse Pronuclear Injection. Image from Tulane Transgenic Mouse Facility

The first transgenic livestock were produced in 1985 using pronuclear microinjection as the delivery modality and while technically challenging and relatively inefficient (1-3% transgenics) it was more or less reliable.  This was essentially the only way to produce transgenic animals for the next decade.

Of course, this is exactly how transgenic insects were created during the same time period but while alternative modalities were developed in the mid 1990’s for animals that obviated the need for pronuclear microinjection, insect scientists are still stuck with embryo microinjection as the only delivery modality.

Somatic Cell Nuclear Transfer

During the 1990s animal scientists invented somatic cell cloning, somatic cell nuclear transfer, lentivirus-based vectors and highly active transposon-based vectors, and eventually in the 2000s the ‘invention’ of induced pluripotent stem cells.  These advances went a long way to democratizing the creation of transgenic animals and this was highly impactful, enabling significant advances in the laboratory research and the production of engineered livestock with commercial potential.

No such democratization has occurred in insect science and today, although we have an abundance of genetic technologies that can be introduced into insect genomes – a collection of technologies that likely rivals what is available for animals, 35 years after the first transgenic insect was created, the delivery modality has not changed.  If you want to create a transgenic or otherwise genetically modified insect you will have to solve the embryo microinjection problem.

Murray and Maga (2016) pose and then answer the question – with such robust technologies now available ‘what is the bottleneck limiting the adoption of genetically engineered, and potentially gene edited, animals into agriculture and the marketplace?”  Their short answer to this that it is largely a ‘political’ problem.

Transgenic Pig Image from doi:10.3390/genes3040615

Even given the compelling challenges of having to feed 9 billion people or more by 2050 and the demand this creates for improved production and distribution systems in agriculture, animals bred and modified using contemporary genetic technologies have yet to reach consumers.

Again, the parallels to insect science are notable.

Murray and Maga (2016) characterize the U.S. regulatory system as dysfunctional and unable to make decisions.  In their view, one important source of problems is the inordinate amount of emphasis that is placed on the ‘processes’ used to ‘create’ new livestock instead of the actual phenotype of the animal.

Gene-editing technologies, which relies on ‘processes’ such as somatic cell cloning or pronuclear microinjection, result in animals that are phenotypically indistinguishable from conventionally bred animals yet they might be and likely will be, at least in the near term, considered a ‘GMO’.

Transgenic salmon. Image credit – AquaBounty.

This kind of muddled system, according to Murray and Maga (2016), needs to be reformed and they outline a number of interesting recommendations but fundamentally they advocate a system that focuses on ‘products’ and not ‘processes’.

Moving insects produced in the laboratory to the field must deal with the same muddled system.

Murray, J. D., Maga, E. A., 2016 Genetically engineered livestock for agriculture: a generation after the first transgenic animal research conference. Transgenic Res: 1-7 doi: 10.1007/s11248-016-9927-7

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