MOO-ving Forward: Transgenic Cows as Insulin Producers

by: Sheena Gaudia | Chromoplexy & Jewel Christi Umali | Chromoplexy

IMAGE CREDIT: Getty/iStockphoto/Peter Cade

One key component in diabetes research is insulin, a hormone that regulates blood glucose levels by facilitating glucose uptake into muscle, fat, and liver cells, where it is utilized for energy. When insulin production is insufficient, blood glucose levels can rise to abnormally high amounts, leading to diabetes. This is where biotechnology can offer innovative solutions in addressing diabetes, particularly through advanced insulin production and continuous glucose monitoring. Dr. Matthew Wheeler and his team from the University of Illinois Urbana-Champaign and the University of São Paolo conducted ground-breaking research on the production of human insulin in the milk of transgenic cows. Cows have a long lactation period and make large amounts of milk; therefore, recombinant protein expression in milk is advantageous. 

Developing Transgenic Cows

The scientists genetically engineered a cow by introducing human DNA coding for proinsulin—a precursor form of insulin. The gene was inserted via a mammary gland-specific expression vector into an immortalized cell line of mammary epithelial cells and bovine fibroblasts. In vitro screening was then performed to ensure only modified cell lines would be used for somatic cell nuclear transfer (SCNT). The selected cow cells were then fused with bovine oocytes with their chromosomes extracted, and the resulting specialized embryos were implanted into a recipient cow. After a successful birth of a female calf, it was hormonally induced to lactate to allow the evaluation of proinsulin expression using Western blotting analysis and mass spectrometry. The results revealed that transgenic cow's milk contained more human insulin than proinsulin and that the existence of protease enzymes could convert proinsulin to insulin. This marks a significant step toward developing human insulin-producing cows.

Challenges and Concerns

Despite these encouraging findings, issues still need to be resolved concerning the production of insulin-rich milk. One major challenge was the presence of insulin-degrading enzymes, which appear to break down insulin and lower its concentration. Additionally, attempts to impregnate the transgenic cow have yet to be successful, more likely due to the limitations of the SCNT technique than the transgenesis. Some individuals may experience unexpected allergic reactions that require close observation and testing. Large-scale insulin production would require optimizing the production process and ensuring the stability of recombinant protein in milk. In addition, drawbacks such as the general public’s resistance to genetically engineered animals could affect the production’s marketability and acceptance in the healthcare industry. 

Future of Proinsulin-Producing Cows

Though there are hurdles to overcome, the promising advantages of using transgenic cows for human insulin production and diabetes treatment are significant. If the process is refined, it could provide a cost-effective method for producing insulin, especially for diabetes patients in areas with limited resources. Advancements in genetic modification could enable the development of insulin analogs that act more quickly or have longer effects, providing patients with alternative treatment options.

Dr. Wheeler and his team remain optimistic that research on transgenic cows will continue progressing. With a conservative estimate of 28,818 units of insulin per liter of milk that can be produced, and given that certain cow breeds make about 40-50 liters of milk per day, an astounding amount of insulin can be yielded.

“I could see a future where a 100-head herd [...] could produce all the insulin needed for the country,” lead scientist Wheeler said about the future use of transgenic cows. “And a larger herd? You could make the whole world’s supply in a year.”

With continued research, refinement of the production, and development of science-based regulatory frameworks, the future of human insulin production from transgenic cows could soon become a reality to support diabetes care.

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This article was originally published in GENEWS November 2024 Issue