Can cows be engineered to produce human insulin proteins in their milk?

Scientists are on the trail of a new discovery: Can cows be engineered to produce human insulin proteins in their milk? A genetically modified cow has produced the much-needed human insulin protein in its milk. Scientists are excited by this development and believe that a herd of such cattle could solve the problem of insulin supply.

If such a herd can be built – however remote that may be – it could compete with current production using genetically modified yeast and bacteria.

Insulin and its role in diabetes was discovered in 1921 and many diabetics were treated with insulin produced from the pancreas of cattle and pigs. But in 1978, ‘human’ insulin protein was produced for the first time from genetically modified E. Coli bacteria. The E. Coli bacteria, as well as yeast, which has the same process as the bacteria, are today the main source of treatment.

Can cows be engineered to produce human insulin proteins in their milk?

Yes, genetically modified cows can be engineered and produced so that they can produce human insulin proteins in their milk. This was proven in a study by a team of researchers from the University of Illinois Urbana-Champaign. The researchers achieved this result by inserting a specific human DNA segment into the cell nuclei of cow embryos. With this method, the use of cows to supply insulin has the potential to compete with current production methods using genetically modified yeast and bacteria.

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Turning to cows for insulin supply is not new, but a new study marks the first time ‘human’ insulin production has been successful in genetically modified cattle.

The research team, led by animal scientist Matt Wheeler from the University of Illinois Urbana-Champaign, inserted a specific human DNA segment encoding pro-insulin (a protein that is converted into insulin) into the cell nuclei of 10 cow embryos, which were then implanted into the uteruses of normal cows.

An innovative approach to hormonal induction

Only one of these genetically modified embryos developed into a pregnancy, leading to the birth of a transgenic calf. When it reached maturity, several attempts were made to impregnate the genetically modified cow using artificial insemination, in vitro fertilization or even the old-fashioned way. None were successful, but the team notes that this may have had more to do with how the embryo was created than the fact that it was genetically modified.

Finally, using an undisclosed method attributed to animal reproduction technologist Pietro Baruselli of the University of São Paulo, they managed to make the cow lactate through hormonal induction.

The cow did not produce as much milk as during pregnancy, but the small amount of milk it produced over a month was analyzed using western blotting and mass spectrometry to look for specific proteins.

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Blotting revealed two bands with similar molecular masses to human proinsulin and insulin, which were absent in the milk of non-transgenic cows . Mass spectrometry showed the presence of C-peptide removed from human proinsulin in the process of insulin formation, suggesting that enzymes in cow’s milk may have converted ‘human’ proinsulin into insulin.

Scalability and future perspective

“Our goal was to get proinsulin and purify it into insulin and go from there. But the cow basically processed it itself. It converts biologically active insulin to proinsulin by about a third.

In 2014, a similar genetic modification was carried out in mice, whose milk contained up to 8.1 grams of human proinsulin per liter. Comparable concentrations were not reported in this new study, but that hasn’t stopped Wheeler from considering scaling up.

A typical unit of insulin is 0.0347 milligrams, so if each cow could produce one gram of insulin per liter of milk, as Wheeler suggests, that would mean 28,818 units of insulin.

“You would need specialized, high-health status facilities for cattle, but that’s nothing too unusual for our well-established dairy industry. I can see a future where a 100-head herd… could produce all the insulin needed for the country, but what about a larger herd? You could supply the whole world in a year .”

References: Cockerill, J. (2024, March 18). Scientists Engineer Cow That Makes Human Insulin Proteins in Its Milk : ScienceAlert. ScienceAlert. https://www.sciencealert.com/scientists-engineer-cow-that-makes-human-insulin-proteins-in-its-milk
Monzani, P. S., Sangalli, J. R., Sampaio, R. V., Guemra, S., Zanin, R., Adona, P. R., Berlingieri, M. A., Cunha‐Filho, L. F. C., Ocampo, I. Y. M., Pirovani, C. P., Meirelles, F. V., Wheeler, M. B., & Ohashi, O. M. (2024, March 1). Human proinsulin production in the milk of transgenic cattle. Biotechnology Journal. https://doi.org/10.1002/biot.202300307