A team of scientists from Brazil made history by successfully developing the first cow in the world capable of producing milk which contains human insulin. This promising work could help people living with diabetes worldwide, increasing insulin production while reducing costs.¹

Key terminology

Let’s take a closer look at some of the key terminology before we review this important and revolutionary advancement.

Transgenic

•  A transgenic animal is one whose genetic material has been changed by the addition of one or more genes from another species of animal. Transgenic organisms (animals, cells or plants) are created in laboratories for scientific research purposes²

Diabetes

• Known medically as diabetes mellitus, diabetes is a chronic condition in which the pancreas does not produce enough insulin, a hormone used to control our blood sugar levels. This can cause blood sugar levels to become too high which can lead to health complications (such as eye problems, kidney failure, heart disease, nerve damage etc)³
• There are two main types of diabetes:
  • Type 1 diabetes = also known as insulin-dependent diabetes, type 1 diabetes is a condition in which the immune system destroys the cells in the pancreas that produce insulin. It is a lifelong condition³
  • Type 2 diabetes = in this condition, the pancreas does not make enough insulin to regulate blood sugar levels, or it does not use insulin effectively to regular blood sugar levels. It is the most common type of diabetes³
• Other diabetic conditions include: gestational diabetes (high blood sugar during pregnancy), and non-diabetic hyperglycaemia (also known as pre-diabetes)³

Insulin

• A hormone produced by the pancreas that reduces blood sugar levels and helps maintain normal blood sugar levels. Synthetic versions of human insulin are used in the treatment of diabetes.
• The building block for insulin is the protein, proinsulin

Viral vector

• A tool for transferring genetic material into cells. Lentiviruses, for example, are responsible for diseases like HIV. They insert their DNA into human cells and can be used as vectors in gene therapy

Mammary gland

• Also called the breast, the mammary gland consists of tissue and fat, and it functions to produce milk for offspring

Context

Diabetes is one of the most common diseases in the world, and also one of the most rapidly rising, particularly in low- and middle-income countries.⁴ As outlined by the World Health Organisation (WHO), the number of people with diabetes rose from 108 million to 422 million between 1980-2014, and the mortality rate for diabetes rose by 3% between 2000-2019.⁴ Type 2 diabetes is by far the most prevalent, representing c.95% of all cases.⁴ The high demand for insulin worldwide has led to shortages and rising costs. A pioneering biotechnological study has been carried out to address these issues, with ground-breaking results. 

About the study¹

A joint initiative between the Universidade de São Paulo and the University of Illinois Urbana-Champaign (UIUC), this study was designed to help combat the issues of insulin supply and the rising costs associated with it worldwide. 

The study involved the following key steps:

• Human DNA for proinsulin was inserted into the cells of 10 cow embryos through biotechnological methods using lentiviral vectors. This DNA was modified so that it would only be expressed in mammary tissue
• The embryos were implanted into the uteri of normal cows in Brazil
• Of these, 1 transgenic calf was produced 
• When the calf had matured into a cow, and failed to get pregnant through various means (including natural mating, artificial insemination, and in vitro fertilization), the researchers stimulated milk production using hormones
• This yielded small quantities of milk, in which both proinsulin and insulin were found

A technique called western blotting (used to separate and identify proteins based on weight) was employed. It indicated the presence of proinsulin and insulin proteins in the transgenic cow’s milk. Another scientific technique called mass spectrometry (used to determine the mass of different molecules) showed that there was more human insulin than proinsulin in the milk, and highlighted the presence of enzymes in the milk also.

Key findings

The results showed that:

• The milk contained the precursor to insulin (proinsulin) and human insulin
• The milk contained more insulin than proinsulin
• The milk also contained protease enzymes which could either be converting the proinsulin into insulin, or degrading the proteins

What makes the transgenic cow revolutionary in diabetes treatment?

The brown bovine is at the centre of this ground-breaking work in diabetes management and treatment. As noted by Animal Sciences Professor Matt Wheeler, the lead author on this study published in the Biotechnology Journal in March 2024,¹ “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.”⁵

Although insulin has been produced in other organisms, such as bacteria, yeast, and mice, using larger animals like cows can help produce insulin on a larger scale.¹ This could be potentially revolutionary in scaling up the production of insulin worldwide, making it more available for diabetes patients and reducing costs. 

What next?

One of the key drawbacks of this study is that the cow did not get pregnant, but rather her milk production (or lactation) was induced using hormones. This means that compared to normal lactation after pregnancy, a much smaller amount of milk was produced. As the volumes were small, it is hard to determine or predict exactly how much insulin could be produced. In addition, the milk contained protein-degrading enzymes that may be affecting the quantities of insulin in the milk.¹ Further research is needed in which the transgenic cow can be successfully impregnated to produce higher quantities of milk for analysis.¹

FAQ’s

What are the first signs of being a diabetic? 

The following are symptoms of diabetes:

• Being very thirsty
• Urinate more often, especially at night
• Losing weight without trying
• Being very hungry
• Having blurry vision
• Feeling very tired
• Having numb or tingly hands or feet
• Having very dry skin

When should I get help?

If you experience any of the symptoms of diabetes listed above, see your GP for a blood sugar test.

Can human insulin be produced by other transgenic organisms?

Yes, the commercial production of human insulin is with a bacteria called Escherichia coli (or E.coli). This is done through a process of genetic engineering.

How did people get insulin before transgenic bacteria?

E.coli was used to commercially generate human insulin in the late 1970s. Before this time, doctors used insulin from animal sources (mainly from the pancreas of cows and pigs) to treat diabetes.

How do human and cow insulin differ?

It has to do with the structure of the protein making up the insulin hormone. Cow (or bovine) insulin has three amino acids, the building blocks of protein, that differ from human insulin.

What is the world’s first transgenic cow?

Rosie, the first transgenic cow, was created in 1997. She produced human-protein enriched milk.

How is biotechnology used in insulin?

Scientists have developed recombinant DNA, which is where a human gene is inserted into the genetic material of bacteria. To produce insulin, the human DNA that codes for the protein insulin is inserted into the bacteria, allowing it to produce insulin.

What is the benefit of having insulin produced by biotechnology?

Insulin produced by biotechnological means it is identical to the human insulin that our pancreas produces. Engineered insulin therefore does not typically elicit an immune response. Biotechnology also allows the production of insulin at scale.

Summary

Diabetes is a serious chronic condition in which blood sugars level become too high as the pancreas cannot secrete insulin or use insulin effectively to reduce blood sugar levels. If left untreated, diabetes can lead to many health complications, such as eye problems and heart disease. A pivotal 2024 study in Brazil used biotechnology to create a transgenic cow capable of producing human insulin (and its building block, proinsulin) in its milk. Further research is needed to verify and enhance these findings. Nonetheless, this ground-breaking work could generate a novel way of mass insulin production for diabetes patients which could reduce shortages and costs.