12.3 Genetically Modified Animals

Animal breeding that focuses on productivity may compromise livestock’s immunity aginst diseases, possibly via at the major histocompatibility complex (i.e., MHC complex) - hence, high density farming also fuels the spread of diseases.

For this reason, large doses of antibodies have been used throughout farming.

12.3.1 In the One Health context…

Some examples of genetically modified animals include:

1. Chickens that are resistant to influenza
2. Cows that have glycyl-glycine endopeptidase lysostaphin in their milk to combat S. aureus infections
3. Cows that secrete human proteins in their milk
4. Pigs whose organs are more suitable for organ transplant
5. Goats that produce blood clot-dissolving agents
6. Reduction or the elimination of disease vectors (e.g., mosquitoes).
7. Cattle that are resistant towards BSE?

12.3.2 Xenotransplantation

There is a growing demand for organ transplants, yet the donor pool remains small.

Xenotransplantation is the act of using animal organs for organ transplants - this is a cost effective and a less ethical approach.

However, the issue is that animal organs may have viral genes in their genome and that the patient may have immune reactions against the non-human organ.

12.3.3 Case study 1: kidney xenotransplants with “10-GE pigs”

These “10-GE” pigs have the following modifications to their genomes - all of which are human genes:

1. Two complement inhibitor genes: hDAF and hCD46
2. Two anticoagulant genes: hTBM and hEPCR
3. Two immunomodulatory genes: hCD47 hHO1
4. Knockout of carbohydrate antigens and pig growth hormone receptor gene

“10-GE” pigs are suitable as a universal donor - these pigs have no red blood cell antigens.

12.3.3.1 Key data findings

Figure 12.14: Kidney Transplant on a Brain-Dead Human

When the kidney was xenotransplanted into a human, the kidney was able to remain functional for 74 hours with no evidence of cellular rejection.

This shows that kidney xenotransplants from “10-GE” pigs are a safe solution to suitable xenotransplantation

12.3.4 Case study 2: gene drives to reduce female mosquitoes’ fertility rates

This study relies on a CRISPR-Cas9 gene drive system that is only active in the germline of female mosquitoes. By targeting a reproductive gene in a female mosquito in a generation, the infertility becomes propagated throughout subsequent generations.

Figure 12.15: Transmission of Infertility on Mosquito Populations

Transmission rates to the mosquitoes’ offspring reached about 91% to 99%.

12.3.4.1 Significance and controversies of gene drives

This is regarded as a significant piece of technology to control pests and invasive species - it is regarded as the ultimate weapon to control mosquito vectors.

“Field trials” of gene drives are now starting in African countries.

However, there are concerns regarding gene drives, notably its use as a weapon.

12.3.4.1.1 Modifying human genes - a pandora’s box?

In 2018, a maverick researcher claimed to be have genetically altered babies to be less prone to HIV infections.

Could this be a Pandora’s box of some sort?

12.3.4.1.2 Gene-edited baby controversy

In November 2018, a Chinese scientist announced that he created the world’s first gene-edited babies. According to the scientist, the babies’ father was HIV positive and hence, the he aimed to reduce the father’s babies’ risk to HIV via a mutation the target gene CCR5.

The CR5 gene protein helps the HIV virus gain entry into the cell; hence, the scientist disabled the gene using CRISPR-Cas9 in two zygotes.

Reactions to the scientist’s work was swift and condemning:

1. His technology was premature with varying success rates
2. He exposed the children to unnecessary health risks
3. Possible mutations to other genes?
4. He violated bioethics principles

Not only did China rule that prior approval is needed for such studies, but the scientist also did not publish a paper.

As of now, the whereabouts of the children are unknown, but the scientist was sent to jail for three years.