Good news for diabetics! Can this cow produce milk containing human insulin? This cow is really amazing →

Compiled by: Gong Zixin

Diabetes mellitus, caused by either insulin deficiency (type 1) or insulin resistance (type 2), has become one of the fastest growing global health emergencies. An estimated 537 million people are living with diabetes in 2021, a number projected to reach 783 million by 2045. The global demand for human insulin for the treatment of diabetes is growing.

Now, a humble cow from southern Brazil has made history by becoming the first genetically modified cow capable of producing human insulin in its milk.

The study, led by researchers at the University of Illinois at Urbana-Champaign and the University of São Paulo, could herald a new era in insulin production that could one day help people with diabetes overcome drug shortages and high costs. The study was published in the Journal of Biotechnology.

"Mother Nature designed the mammary gland to be a very efficient factory for making proteins. We can harness this system to produce a protein that could help hundreds of millions of people around the world," said Matt Wheeler, a professor in the UC Department of Animal Sciences.

The researchers inserted a human DNA fragment encoding proinsulin (the protein precursor of the active form of insulin) into the nuclei of 10 cow embryos. These genes were implanted into the uterus of normal cows and a transgenic calf was born. Thanks to the latest genetic engineering technology, the human DNA was targeted for expression only in mammary tissue - the process by which the gene sequence is read and translated into a protein product.

Schematic diagram of the lentiviral vector constructed for mammary gland-specific human insulin expression and restriction mapping analysis

Wheeler noted that using DNA structures unique to mammary tissue means there is no human insulin circulating in the cow's blood or other tissues, and it also takes advantage of the mammary gland's ability to produce large amounts of protein.

When the cows were mature, the team tried to conceive them using standard artificial insemination techniques, but without success. They used hormones to stimulate the cows' first lactation, but the milk production was less than after a successful pregnancy. Surprisingly, human proinsulin and insulin could be detected in the milk.

Transgenic analysis

“Our goal is to make proinsulin, which starts with purifying it into insulin. But this cow basically processes it herself, and it produces about a 3:1 ratio of bioactive insulin to proinsulin. The mammary gland is really amazing.”

So how much insulin does a typical lactation produce? Conservatively, if a cow produces 1 gram of insulin per liter, the typical unit of insulin is equal to 0.0347 mg, which means that each gram is equivalent to 28,818 units of insulin. This is just 1 liter, and a typical Holstein cow produces 40 to 50 liters of insulin per day, so you can do the math.

Mass spectrometry analysis

The team plans to clone the cow again and is optimistic that they will have greater success in getting the next generation pregnant and completing the lactation cycle. Eventually they hope to create transgenic bulls to mate with females to create transgenic offspring that can be used to establish a specific herd. Wheeler said even a small group of transgenic yeast and bacteria could quickly outperform existing methods of producing insulin, and would not require the establishment of high-tech facilities or infrastructure.

“To produce insulin in milk on a large scale would require specialized, well-established facilities, but that’s nothing special for the established dairy industry,” Wheeler said.

Before genetically modified cows can provide insulin to diabetics around the world, an effective system needs to be in place to collect and purify the insulin product and get FDA approval. Wheeler believes that day will come. "I can see a future where a herd of 100 cows, the size of a small dairy farm in Illinois or Wisconsin, could produce all the insulin the nation needs. A much larger herd could produce the world's supply of insulin in a year."