Researchers for the first time ever have genetically altered a cow to produce insulin in its milk. The breakthrough is cause for celebration for the more than 3.6 million Americans with diabetes that use insulin to control their condition. Because global demand is so high, insulin is often expensive and can be difficult to obtain. The hope is that having another mechanism to produce the vital hormone can alleviate both high prices and availability issues.
According to study leader Matt Wheeler, a professor of animal sciences at the University of Illinois Urbana-Champaign, “Our goal was to make proinsulin, purify it out to insulin and go from there.” However, Wheeler says the cow basically processed it herself. “Mother Nature designed the mammary gland as a factory to make protein really, really efficiently,” explained Wheeler. “We can take advantage of that system to produce a protein that can help hundreds of millions of people worldwide.”
Diabetes is a chronic disease that disrupts how the body metabolizes blood sugar. Normally, a rise in blood sugar signals the pancreas to release insulin. But in one form of diabetes, type 1, we now know that the pancreas produces little or no insulin; in type 2, the pancreas may produce insulin, but the body can’t use it effectively. In either case, the body’s glucose levels rise, eventually leading to dangerous circulatory, nervous, and immune system problems.
The injectable insulin diabetics use today is produced by inserting a lab-built form of the human insulin gene into bacterial DNA. Placed into large fermentation tanks, the bacteria use the gene to produce human insulin, which is harvested and purified for human use.
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 into normal cows, resulting in one transgenic calf. Once mature, 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. While the cow produced less milk than a successful pregnancy would have produced, it not only had detectable levels of proinsulin but also insulin itself, which surprised the researchers.
The insulin produced was just a few grams per liter, though the researchers note that they don’t know how much insulin production would be typical as this is a first-of-its kind breakthrough. Still, by Wheelers calculations, it would amount to a lot of insulin for a Holstein cow that can produce 40 to 50 liters of milk per day.
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 will be to clone the cow and hopefully have better luck with pregnancy and full lactation. 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.” The full study, “Human proinsulin production in the milk of transgenic cattle,” is published in Biotechnology Journal HERE. (Sources: University of Illinois Urbana-Champaign, Biotechnology Journal, New Atlas)
