Soaring insulin costs? Cows could help.

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The high cost of insulin in the US has inspired scientists to hunt for new ways to affordably manufacture the medication — including a genetically engineered cow that produces insulin in its milk.

The history of insulin

Insulin is a protein made by the pancreas to convert glucose, a type of sugar, in your blood into energy for your cells. 

People with diabetes don’t make enough insulin (called type 1) or their bodies don’t use it effectively (type 2). As a result, they’re at risk of chronically high blood sugar — and the many serious health problems associated with it, such as heart damage, vision loss, and kidney failure. 

While reports of people with diabetes can be found in records more than 3,000 years old, it wasn’t until the 1800s that scientists finally linked the condition to the pancreas. By the early 1900s, they’d discovered that pancreatic cells excreted a substance that prevented diabetes. 

They named it “insulin” and figured out a way to extract and purify it from the pancreases of cattle and pigs — and two tons of pig pancreases were needed to extract just eight ounces of the precious drug. 

Doctors then started using it to treat people with diabetes, turning what had previously been a death sentence into a somewhat manageable condition.

“Insulin does not belong to me. It belongs to the world.”

Frederick G. Banting

In 1923, three of those early insulin researchers — Frederick G. Banting, Charles H. Best, and James B. Collip — were issued US patents for insulin and their methods for purifying it, which they sold to the University of Toronto (UT) for just $1 each, citing their hope that no one who needed the drug would ever have to go without it.

“Insulin does not belong to me,” said Banting. “It belongs to the world.”

So, why were some Americans recently spending more than $1,000 per month on insulin and, in some cases, dying because the high cost forced them to ration their medicine?

Money matters

Soon after the discovery of insulin, UT began issuing manufacturing licenses to pharmaceutical companies, and for the next 50 years, those companies focused on looking for ways to further refine insulin from animals.

Then, in the 1970s, researchers made a breakthrough that changed everything: they learned how to insert human DNA into bacteria or yeast cells to get them to produce highly pure and entirely human insulin. 

This created an entirely new supply of the drug that could be manufactured as needed, rather than the supply fluctuating with the ups and downs of the market for meat.

In 1982, the FDA approved the first of these insulins —  Eli Lilly’s Humulin — and by the 1990s, researchers had learned how to tweak the genes to create specialized human insulin “analogs,” versions of the hormone that were longer lasting or faster acting.

By 2006, the US had completely stopped producing animal insulin for human use, leaving just these new forms available for people with diabetes, and complicated manufacturing processes discouraged all but a few companies from attempting to develop them.

These few companies have been able to repeatedly extend their patents on the drugs, too, by making tiny changes to the formulations. This practice is called “evergreening,” and it discourages drug manufacturers from marketing generics of older out-of-patent formulas — there’s always an updated formula available that doctors are more likely to prescribe.

When the first human insulins and insulin analogs were approved in the US, the meds were generally affordable, but by the 2000s, just three companies dominated the US insulin market — Eli Lilly, Sanofi, and Novo Nordisk — and they started to take advantage of the limited competition to significantly raise their prices. 

By 2022, 8.4 million Americans were relying on insulin — and they were paying more than nine times as much per unit as people in other high-income nations, according to a RAND report funded by the US Department of Health and Human Services.

The US government finally began taking action. 

In 2022, Congress passed the Inflation Reduction Act, which capped the price of insulin at $35 per month for people on Medicare, and in his 2024 State of the Union address, President Joe Biden said his goal is to cap the cost of insulin at $35 per month for all Americans.

The approval of new generic and biosimilar insulins in recent years is also helping address costs, but the average price for patients today is still 30% higher than it was a decade ago, according to data from GoodRX. 

Researchers, though, believe that we could soon come up with some other affordable, scalable sources of the life-saving medication, like… cows.

Milk meds

Rather than inserting the human insulin gene into bacteria or yeast, researchers at the University of Illinois Urbana-Champaign (UIUC) and the University of São Paulo in Brazil spliced the gene coding for proinsulin — the precursor for insulin — into cow embryos. 

They then implanted 10 embryos into surrogate cows, leading to one successful birth.

When that calf was old enough, they tried to stimulate lactation by artificially inseminating her. When that didn’t work, they turned to hormone injections. This caused the cow to produce milk, though not nearly as much as she would have made if she were pregnant.

When the team tested the milk, they found about 3 grams of proinsulin and insulin in each liter.

“Our goal was to make proinsulin, purify it out to insulin, and go from there,” said Matt Wheeler, an animal sciences professor at UIUC and lead author of a paper describing the cow.

“But the cow basically processed it herself,” he continued. “She makes about three to one biologically active insulin to proinsulin. The mammary gland is a magical thing.” 

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

Matt Wheeler

The team plans to attempt to clone their insulin-producing cow and is hopeful they’ll be able to successfully impregnate the clone, unlocking milk production. Until that happens, they can’t say for sure how much proinsulin and insulin might be obtained through typical lactation. 

If the animal’s milk contains just 1 gram per liter, though, the impact could be huge — the typical dairy cow produces 40-50 liters of milk per day. 

A lot of factors would go into the final sale price of cow-sourced insulin — the cost of extracting and purifying the insulin in the milk, for example — but the researchers believe cows could be a viable way to produce large amounts of the life-saving protein.

“Mother Nature designed the mammary gland as a factory to make protein really, really efficiently,” said Wheeler. “We can take advantage of that system to produce a protein that can help hundreds of millions of people worldwide.”

If the team is able to successfully impregnate their cloned cow and induce natural lactation, the next step will be creating bulls with the human insulin gene and seeing if they can get them to mate with the gene-edited cows to create insulin-producing offspring.

After all of that, the researchers would still need to work with regulators to get the new source of insulin approved. Still, they’re hopeful their research could one day result in herds of insulin-producing cows capable of supplying the medication to anyone who needs it.

“With regard to mass-producing insulin in milk, you’d need specialized, high-health-status facilities for the cattle, but it’s nothing too out of the ordinary for our well-established dairy industry,” said Wheeler. “We know what we’re doing with cows.”

The insulin-producing cow

The big picture

Insulin-producing cows aren’t our only hope for diversifying the insulin market.

Houston biotech startup rBio has developed a strain of bacteria for producing biosimilar insulins — insulins that are very similar but not exact copies of ones already approved by the FDA — that yields twice as much of the protein as existing methods.

rBio is now preparing for clinical trials of its first product, R-biolin, and if it performs well, the startup is hopeful the increased yield will mean it can sell its insulin for significantly less than current options.

Nonprofit drugmaker Civica Rx is also developing several insulin biosimilars in the hope of cutting costs. In 2023, the state of California signed a deal with the group to make those insulins available to residents for $30 per vial, if and when they’re approved.

“The more companies that are making insulin and the more options patients have available, the less expensive it’s going to become over time,” Robert Lash, a diabetes expert and CMO of the Endocrine Society, told WIRED.

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