First cow to produce human insulin in its milk created in Brazil

Scientists have created a cow which can produce human insulin in its milk.

The animal is transgenic – meaning DNA from another species, in this case human, was introduced into it through genetic engineering.

The research was led by Matt Wheeler, professor in the Department of Animal Sciences at the University of Illinois in the US, who says it takes advantage of the special factors of the mammary gland.

“Mother Nature designed the mammary gland as a factory to make protein really, really efficiently.

“We can take advantage of that system to produce a protein that can help hundreds of millions of people worldwide.”

The research described in a new study in Biotechnology Journal.

According to the World Health Organization, about 422 million people worldwide have diabetes. Type 1 diabetes occurs when the body cannot produce its own insulin, whereas type 2 occurs when the body doesn’t make enough insulin and becomes resistant to it.

The insulin-producing cow is a ‘proof-of-concept’ that could one day be scaled up to produce enough insulin to supply the world’s diabetics, eliminating scarcity and high costs associated with it.

“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. And a larger herd? You could make the whole world’s supply in a year,” Wheeler claims.

Wheeler’s colleagues at the University of São Paulo in Brazil inserted a segment of human DNA coding for proinsulin – the precursor of the active form of insulin – into the cell nuclei of 10 cow embryos. These were implanted in the uteruses of normal cows, which resulted in the birth of one transgenic cow.

“In the old days, we used to just slam DNA in and hope it got expressed where you wanted it to. We can be much more strategic and targeted these days,” says Wheeler.

“Using a DNA construct specific to mammary tissue means there’s no human insulin circulating in the cow’s blood or other tissues. It also takes advantage of the mammary gland’s capabilities for producing large quantities of protein.”

A photograph of a small light-brown coloured calf left, and photograph of an older man in a suit right.
Matt Wheeler (right) helped develop the first transgenic cow to produce human insulin in her milk (left). Credit: University of Illinois Urbana-Champaign

Attempts at impregnating the cow once she had reached maturity were unsuccessful, so the team stimulated lactation using hormones.

“Our goal was to make proinsulin, purify it out to insulin, and go from there. But the cow basically processed it herself. She makes about three to one biologically active insulin to proinsulin,” Wheeler says.

The insulin and proinsulin were expressed at a few grams per litre of milk. But because the milk volume was smaller than expected due to the hormone-induced lactation, the researchers can’t say exactly how much insulin would be made in a typical lactation. 

Wheeler says the typical unit of insulin equals 0.0347 milligrams and, conservatively, if a cow could make 1 gram of insulin per litre “that means each gram is equivalent to 28,818 units of insulin.”

“And that’s just one litre; Holsteins can produce 50 litres per day. You can do the math,” he says.

The insulin and proinsulin would need to be extracted from the milk and purified for use in humans.

The team now has plans to re-clone the cow and attempt pregnancy and full lactation cycles in the next generation. Eventually, they hope to create transgenic bulls to mate with the females, creating transgenic offspring that can be used to establish a purpose-built herd. 

Wheeler says even a small herd could quickly outcompete existing methods — transgenic yeast and bacteria — for producing insulin.

“With regard to mass-producing insulin in milk, you’d need specialised, high-health-status facilities for the cattle, but it’s nothing too out of the ordinary for our well-established dairy industry,” Wheeler says.

“We know what we’re doing with cows.”

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