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  • Scientists at AgResearch have generated transgenic cows that produce therapeutic proteins in their milk. Here, we explain the advantages and disadvantages of using transgenic technologies to produce proteins.

    What are therapeutic proteins?

    Therapeutic proteins are used to treat human diseases. They include hormones, antibodies, vaccines, growth factors and blood clotting factors.

    Rights: Acknowledgement: Biopharm International, Sandoz

    Therapeutic protein production facility

    Large or complex therapeutic proteins are made in mammalian cells grown in large sterile vats. These facilities are expensive to set up and can only produce a limited amount of protein.

    Making therapeutic proteins

    Therapeutic proteins are usually synthesised in cell-based systems. In these systems, the desired gene is added to a cell, and the cell’s own machinery makes the protein. The 4 systems currently used to make therapeutic proteins are:

    • microorganisms, for example, yeast bacteria or fungi
    • plants
    • mammalian cells
    • transgenic animals.

    Uses of transgenic cows

    Dr Goetz Laible, a senior scientist at AgResearch, explains the various possibilities that transgenic cows offer.

    The cell-based system used for making a particular therapeutic protein depends upon the size and structure of the protein, as well as the amount of protein required.

    Small, simple proteins (like insulin, human growth hormone and interferon) are usually produced in genetically engineered microorganisms. Human insulin, for example, is a small protein consisting of 51 amino acids. Human insulin was first made synthetically in the bacteria E. coli in the late 1970s. It was approved by the USA Federal Drug Administration (FDA) in 1982 and has been available for diabetics since that time.

    Rights: The University of Waikato Te Whare Wānanga o Waikato

    A nerve cell

    The axon of a nerve cell is surrounded by myelin. Myelin helps to conduct signals along the length of the nerve cell.

    Larger, more complex proteins (like antibodies) are usually produced in mammalian cells. Herceptin, the breast cancer-treating antibody, is an example of a large complex protein that is synthesised in mammalian cell culture. To produce this protein, mammalian cells are grown in large sterile vats in nutrient-rich media under strict manufacturing standards. This type of production can be expensive to set up and maintain, making the end product costly. For example, the Herceptin antibody is expensive, with a 12-month course costing up to NZ$100,000.

    The number of therapeutic proteins being developed by the biomedical industry is growing rapidly, and some scientists are predicting that demand for proteins will soon exceed their ability to supply them. Transgenic animals could provide an alternative source of therapeutic proteins to help meet these demands.


    Producing therapeutic proteins in transgenic farm animals is sometimes called ‘biopharming’. Currently, research groups around the world are investigating whether transgenic animals such as goats, cattle, pigs, rabbits and chickens can be used to produce therapeutic proteins. The animals are used as sterile bioreactors to produce large, complex proteins or proteins that can’t be made in other cell systems.

    Making therapeutic proteins in transgenic cows

    Scientists at AgResearch have generated transgenic cows that produce myelin basic protein (MBP) in their milk. MBP is part of the insulating layer that surrounds nerves. In patients with multiple sclerosis, this insulating layer is gradually destroyed, which prevents the nerves from communicating. Treatment with human MBP may help reduce symptoms of multiple sclerosis.

    In a 2018 update, Dr Goetz Laible noted that funding for AgResearch’s biomedical research projects had finished. Dr Laible’s colleague, Medhat Al-Ghobashy, is continuing with the research at Cairo University. In a paper published in 2017, Dr Al-Ghobashy reports that rhMBP from transgenic cow milk may have potential as a vaccine for MS. The research used mice and is still in preclinical applications.

    Advantages and disadvantages of making proteins in cows

    Dairy cows produce large amounts of protein naturally in their milk. Their protein-making machinery makes an excellent ‘biofactory’.

    Rights: Business Wire, GTC Biotherapeutics, Inc.

    Vials of ATryn®

    ATryn® is a biopharmaceutical made by GTC Therapeutics. ATryn® is produced by transgenic goats. It is the first product made in an animal to be approved for use in Europe and the United States.

    The main advantages of making therapeutic proteins in transgenic cows are:

    • capacity – large amounts of protein are produced – the average dairy cow can produce more therapeutic proteins (about 5–10g/L) than mammalian cells in culture (about 1g/L)
    • cost – transgenesis is cheaper than mammalian cell culture
    • scale – it is easy to scale production up or down to meet demand
    • function – proteins are folded and fully functional
    • harvesting – proteins can readily be purified from milk.

    Advantages of making proteins in transgenic cows

    Transgenic cows can produce therapeutic proteins in their milk. Here, Dr Goetz Laible from AgResearch describes the advantages of using transgenic cows over mammalian cell lines.

    The main disadvantages of making therapeutic proteins in cows are:

    • it takes a long time to generate and validate transgenic cows
    • proteins can’t be harvested until lactation begins
    • the transgene may affect the cow, for example, as the transgene inserts randomly into a chromosome, it may disrupt a gene required for an important function.

    The first international biopharming success

    Transgenic cows making myelin basic protein

    Dr Goetz Laible, a senior scientist at AgResearch, describes how the team at AgResearch have generated transgenic cows that produce human myelin basic protein in their milk.

    In June 2006, the first human therapeutic protein made in a transgenic animal was approved for use in Europe and the USA. ATryn®, an antithrombin, is made in transgenic goats. It is used to prevent blood clots in patients with a rare blood disease. A relatively small herd of goats (about 80) can produce enough protein to supply all of Europe.

    Transgenic research in New Zealand

    In April 2010, AgResearch was granted approval from ERMA (the Environmental Risk Management Authority) to continue developing transgenic animals, including goats, sheep and cattle that produce therapeutic proteins in their milk. In its 2017 report to the EPA, AgResearch noted that it had approximately 90 transgenic cows and goats in its containment farm.

    Useful links

    Making human insulin is a resource for schools with an animation showing how insulin is made, from APBI Resources for Schools, UK.

    Read about Dr Goetz Liable and his team's work to knock down beta-lactoglobulin (BLG), a milk whey protein known to be allergenic, in this 2017 New Zealand Herald article.

      Published 24 February 2010, Updated 15 March 2018 Referencing Hub articles
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