There may be an unexpected fix for ongoing shortages of insulin: A brown bovine in Brazil recently made history as the first transgenic cow able to produce human insulin in her milk.

“Mother Nature designed the mammary gland as a factory to make protein really, really efficiently,” explained study leader Matt Wheeler, a professor of animal sciences at the University of Illinois Urbana-Champaign. “We can take advantage of that system to produce a protein that can help hundreds of millions of people worldwide.”

His team, which included scientists from the University of São Paolo, described how they developed the insulin-making cow in a report published March 12 in Biotechnology Journal. 

More testing, a purification system and approval from the U.S. Food and Drug Administration would be needed to put the strategy to work. But insulin produced by transgenic cows could ease shortages that often make the hormone hard to come by for the 8.4 million Americans with diabetes who rely on it to survive. 

“Our goal was to make proinsulin, purify it out to insulin and go from there,” Wheeler said in a university news release. “But the cow basically processed it herself… The mammary gland is a magical thing.”

To produce the transgenic cow, a segment of human DNA was inserted into the cell nuclei of 10 cow embryos. It contained coding for proinsulin, a precursor of the active form of insulin. Through genetic engineering, the human DNA was targeted for expression in breast tissue only.

The altered embryos were then implanted in the uteri of normal cows in Brazil, and one transgenic calf was born. 

Once she matured, researchers used artificial insemination to try to impregnate her. When that failed, they used hormones to stimulate her to produce milk for the first time. 

Though she made less than a successful pregnancy would have produced, the milk not only had detectable levels of human proinsulin but also insulin itself. Researchers didn’t expect that.

Still, the insulin and proinsulin would have to be extracted and purified for use, and each liter of milk contained only a few grams. Researchers don’t know how much insulin would be typical.

But Wheeler did a quick calculation: If a cow could make 1 gram of insulin per liter of milk, and a typical Holstein makes 40 to 50 liters a day, that’s a lot of insulin. 

A typical unit of insulin equals 0.0347 milligrams.

“That means each gram is equivalent to 28,818 units of insulin,” Wheeler said. “And that’s just one liter: Holsteins can produce 50 liters a day. You can do the math.”

The next step is to re-clone the cow. Researchers are hopeful they will achieve greater success with pregnancy and full lactation cycles in the next generation of animals.

Eventually, the goal is to create transgenic bulls, mate them with the transgenic females and create a “purpose-built” herd. Even a small herd could quickly outpace existing methods for insulin production — without any need for highly technical facilities or infrastructure, Wheeler said.

“I could see a future where a 100-head herd, equivalent to a small Illinois or Wisconsin dairy, could produce all the insulin needed for the country,” he said. “And a larger herd? You could make the whole world’s supply in a year.”

More information

The Mayo Clinic has more about using insulin to manage blood sugar.

SOURCE: University of Illinois Urbana-Champaign, news release, March 13, 2024

Source: HealthDay