The Milky way of Medicine: want a cup of drugs?

30 July 2020

Posted by: Mia Rozenbaum

Category: Research & medical benefits

As genetic engineering of animals is becoming easier and cheaper, so is the production of drugs. Transgenic animals made to produce drugs in their milk could bring expensive medicine to the many and the more remote.

It’s the morning, fuzzy eyed and barely awake, you - almost automatically - pour yourself a cup of tea and for the less fortunate a glass of water to take the morning pills. What would you say if instead of water, you had milk that already contained the drugs you needed?

Sounds a bit like science fiction, but for some decades, scientists have been working on way to genetically engineer goats and cows to produce drugs and other useful molecules directly in their milk. Why? I’m sorry to disappoint, it’s more about the money than the comfort of you mornings. Production costs of these molecules would be greatly reduced if you had a living organism capable of painlessly squirting the drugs out, rather than chains of expensive machines and reactions doing the job.

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Researchers can isolate genes of interest, insert them into expression vectors and transfer them to cells or organisms that, in turn, can produce the protein of interest. If the targeted cells are in the mammary glands, the proteins are only produced in the milk, like any other protein already found in this nutritive liquid.

Once created, these transgenic animals can pump out drugs at low cost, just like any other farm animal. And, with the recent advances in new gene-editing techniques like CRISPR-Cas9, swapping and inserting genes, has never been as easy. Creating new transgenic animals in the lab is now faster and cheaper.

"Having an easier way to harness nature's power to produce large quantities of specific proteins in milk could increase the availability of drugs for people who could otherwise not afford these treatments,"

said Ina Dobrinski, a researcher that applied gene therapy to reduce the time it takes to breed large animals capable of producing therapeutic proteins in their milk, to science daily.

In 1997, the first transgenic cow produced milk enriched in human protein alpha lactalbumin, a protein that regulates the production of lactose in the milk of almost all mammalian species. Ever wondered how lactose free milk was produced? You have the answer right here: one way is to use experimental transgenic cows engineered to do so. And the same goes for low-cholesterol milk important for cardiovascular patients.

The list is long.

Researchers have for example managed to produce cows and goats with higher levels of lysozyme, an antimicrobial protein found in human breast milk. The goat milk was proven effective in treating diarrhoea in young pigs and may be used to help prevent human diarrheal diseases that each year claim the lives of 1.8 million children around the world.

"Many developing parts of the world rely on livestock as a main source of food," said James Murray, a UC Davis animal science professor and lead researcher on the study. "These results provide just one example that, through genetic engineering, we can provide agriculturally relevant animals with novel traits targeted at solving some of the health-related problems facing these developing communities."

Equally, a company named as rEVO Biologics, made transgenic goats secreting antithrombin III in their milk, a therapeutic protein used to prevent post-surgical clot formation in patients with hereditary antithrombin deficiency. The beauty is that a small flock of 80 goats can supply this valuable protein for the whole of Europe.

At the moment, rEVO has 600 goats on its 167-acre Massachusetts farm, separated into herds based on which genes they carry. It has had up to 2,000, depending on how many projects it has going. While ATryn is the company’s only product at the moment, it has half a dozen active projects, each with a handful of experimental goats. For example, the company is also working to develop goats that produce monoclonal antibodies.

The most recent example are goats that can produce a common bowel cancer drug, cetuximab, in their milk. Each resulting genetically modified goat could produce about 10 grams of cetuximab in each litre of their milk. And since goats produce about 800 litres of milk every year, each animal can manufacture multiple kilograms of cetuximab in a year. A great step forwards to making the drug more accessible and cheaper. At the moment it is produced by mouse cells that have been genetically engineered to make the monoclonal antibody. This is an expensive, very precise process which means that the drug costs around £3000 a month for a single patient in the UK. And this could be applied to several other cancer therapies worldwide.

The FDA is gradually accepting the use of these milk-produced proteins for human conception and health. In 2009, the FDA approved a genetically altered goat that can make a drug in its milk that prevents fatal blood clots. And in 2014, it approved a drug collected from the milk of lab-bred rabbits to treat hereditary angioedema, a genetic disease that causes body swelling and can be fatal.

Of all the transgenic mammalian bioreactors already produced, goats seem to be the more appropriate model as production of founder animals and operating costs are significantly easier to manage compared to cattle.

Engineered milk could help make improvements to global health, in particular to lesser developed countries where drugs can be hard to access, produce or purchase.

Researchers have also genetically engineered goats to produce a spider protein in their milk, which is then extracted, purified and spun into fibres. Spider silk is one of the strongest materials in nature, tougher than Kevlar and a hundred times stronger than human ligaments. If harnessed, that power could find applications in medicine but also help build bulletproof vests and a number of different resistant and sustainable materials.

Genetically modified organisms, or “pharm animals”, could become the next revolution for makings drugs more accessible and also more sustainable by lowering production costs and increasing production capacities.