8 min read

Milk and Dairy: Microbial Fermentation and Cell-based approach

Abstract: Factory farming for dairy cows is just as unethical and environmentally polluting as meat cows. The total number of farmed cows across the globe is around 1 billion. About 60% of them are attributed towards meat and the rest towards dairy. While plant-based alternatives certainly meet the market demand for vegan market, they don’t completely meet the functionalities of conventional milk such as taste, consistency and nutrient density. The solution may lie in recreating the dairy proteins and other components through microbial fermentation or cell-based approach.

Introduction

Dairy products are probably among the most savoured food across the globe. A rich ~10,000-year history resides behind the evolution of dairy products that bear nutritional value, commercial value, cultural heritage and hard-to-replicate delicacy.

Credits: ThoughtCo

The processing of milk traces its roots to Anatolia, or ancient Turkey, around 8000BC. To kill pathogens and prevent it from spoiling,  mammalian milk was turned into yoghurt, cheese, and butter by harnessing naturally occurring yeast and bacteria. This enabled ancient farmers to store milk products for longer periods.

The adoption of dairy products points to an interesting narrative that shows how technological innovation affected genetic evolution. Humans didn’t have the natural capacity to digest lactose beyond childhood. Given that early humans were embroiled in famines, drinking other mammal’s milk was a plausible source of food to survive for children. However, the genes that enabled some adults to tolerate lactose started to kick in around 6000 BC.

For millennia, milk was mostly either quickly consumed as a beverage or converted to dairy products owing to its perishable nature. But this also meant the risk of pathogen-associated diseases such as tuberculosis, typhoid fever, scarlet fever or diphtheria could be transmitted through raw milk.

But thanks to Louis Pasteur and his innovative method of destroying harmful bacteria through heat, called Pasteurization, milk could be stored for a longer period of time. The idea was first introduced to wine and beer which took its route to milk 20 years later.

Modern dairy farming began in the early 1900s after pasteurization was developed in combination with another innovative but condemnable approach that spearheaded the mass production of milk, namely factory farming. Selective breeding was also introduced to factors farms which lead to the breeding of only certain types of cows that produced milk in large volumes.

Factory farming for dairy cows is just as unethical and environmentally polluting as meat cows. The total number of farmed cows across the globe is around 1 billion. About 60% of them are attributed towards meat and the rest towards dairy. The calves are immediately taken away after birth inducing great distress to the mother cow. While the male calves are killed or sent off to be raised for meat, the female calves are artificially inseminated and lactated in 3 year time period and eventually slaughtered. In addition, dairy cows live in narrow stalls or pens and are denied socialization which causes both physical and psychological distress.

According to stats from ourworldindata, GHG emissions from animal agriculture is 18%, and of which 35% comes from dairy cattle which means roughly 2.5% of emissions comes from the dairy industry. Dairy is also responsible for a quarter of land use, a third of freshwater use and a third of eutrophication.

Bar chart of how much of the world's greenhouse gas emissions (26%); habitable land use (50%); freshwater withdrawals (70%); eutrophication (78%) and total mammal biomass (94%) results from food and agriculture.

Although there is increasing demand for milk alternatives such as soy and rice milk, thanks to the growing popularity of vegan diets, research suggests that conventional milk production has grown 10 % over the last decade in the US alone. Just like meat, the per capita consumption of dairy is also on the rise. Owing to the growing middle-class economy across the globe, there is an increase in disposable income and demand for improved diet.

Plant-based alternatives:

While plant-based alternatives certainly meet the market demand for milk alternatives, they don’t completely meet the functionalities of conventional milk such as taste, consistency and nutrient density. Given that dairy is one of the most loved food products, there is a definite need for clean dairy that can meet all the requirements of dairy, if not offer better functionalities.

Technical Landscape

Cultured Dairy:

The real solution lies perhaps in lab-grown dairy. While hab-grown meat has been getting a lot of attention, lab-grown dairy products have already hit the market. Advances in synbio technology are driving the industry toward providing alternatives to conventionally produced food products. Dairy proteins are being produced in labs, for use in fluid “milk” production and processed dairy products like yoghurt and cheese, to name a few.

There are two ways to grow milk and dairy products in the lab. Both approaches bypass the need for mammals such as cows, sheep or goats in producing milk or dairy products.  

  1. Recombinant protein approach:

Recombinant protein technology is the most-sought after approach.  This method employs synthetic biology wherein milk-producing genes are sourced from mammals and inserted into industrial-fermentation microbes that manufacture specific dairy constituents.

The gene-sourcing technique is non-invasive, usually taken from existing databases. Just like brewing yeast to produce alcohol, this process employs different microbes in controlled environments to create fermentation byproducts, such as casein and whey protein. The microbes could range from prokaryotic systems such as E.Coli, lactic acid bacteria or eukaryotic systems such as mammalian cells, insect cells, yeast, filamentous fungus, and microalgae.

The rough procedure is as follows:

Credits: Legendairy Foods/Formo

The specific DNA sequence responsible for the synthesis of milk proteins is identified and then amplified. It is then inserted into the genome of a host such as yeast and made to grow in a fermentation process. The desired protein such as casein is then separated from the process and purified before blending it with plant-based components to create the dairy product.

By combining these proteins with plant-based fats, dairy products that behave like animal milk can be produced without requiring any animal husbandry. Although producing milk using this approach is definitely more challenging, products such as yoghurt and cheese which are different from fluid milk may be more suitable for using lab-grown casein and whey.

The regulatory environment surrounding the food industry offers possibly one of the biggest challenges in bringing products to market. There has been a heavy backlash against GMOs (genetically modified organisms), particularly in Europe and this may prove to be a tough battle for lab-grown dairy as well.

However, there is a strong argument to be made that although the microbes are genetically modified in the recombinant protein approach, the proteins they produce doesn't contain any modified DNA.

Although startups have successfully engineered microbes to produce smalls amounts of dairy proteins and fats, scaling up production will be difficult and expensive. Even if startups succeed in scaling up production, providing a wide variety of dairy products while mimicking the complexity (say different types of casein) may be the biggest challenge. It is still difficult for scientists to engineer a microbe to make a variety of caseins and the underlying knowledge of which particular proteins provide the best functionality is also not clear.

2. Cell-based approach:

Credits: Turtle TreeLabs

The other strategy is cell-based dairy milk, a process similar to the cellular meat technology where cells can as a factory processing through the lactation media, keep on multiplying, and convert the lactation media into milk.

A broader distribution of steps looks the following:

  1. Sourcing and harvesting stem cells from the milk directly
  2. Differentiating the stem cells in 2D and 3D cultures by introducing growth factors and hormones
  3. Expose these cells to lactation media where these cells multiply and convert the lactation media into milk.
  4. The milk is then analyzed for specific marker genes  and then separated from the media through filtration
  5. The milk is then analyzed for different compositions such as fatty acids, vitamins, minerals and other elements.
  6. Finally, the milk composition is refined to meet the required target. Unlike the recombinant protein approach where individual components need to be created separately, the cell-cultured milk process can produce milk with the right composition of proteins, lipids and carbohydrates found in milk.

While startups have achieved successful results on a small scale, upscaling the technology to the industrial level will be a herculean task. Translating the process from cultured media to bioreactors on a large scale will come with its own set of challenges. The current focus of startups in the cell-based approach has been largely in producing breast milk. If the cell harvesting involves immortalization (manipulated to proliferate indefinitely), the product could be designated as GMO which will further invite regulatory challenges and prolong the commercialization.

Market Landscape

Perfect Day is the leader having raised $300 million in Series C funding to develop its dairy protein portfolio. The company already released a limited sale of ice-creams that involved lab-engineering casein and whey in 2019. The company's claims that manufacturers could use their existing processes and equipment while using Perfect Day's milk proteins to produce cheese, ice cream or any other dairy product

New Culture has raised $5 million to produce animal-free mozzarella leveraging microbial fermentation. Formo, previously called Legendairy Foods, is the first European company to enter the market with the goal of producing milk proteins that can serve as building blocks for dairy products. Change Foods is an Australian startup using microbes to create real dairy proteins, fats, and flavours through precision fermentation. With 2.1 Million $ in funding and having already produced milk caseins and fats, the startup aims to release its products by 2023.

Better Dairy, founded at Entrepreneur First, is a UK startup that is the most recent to enter the lab-grown dairy market having raised 1.6 million Pounds in seed funding to produce animal-free dairy using yeast-based fermentation. Remilk is an Israeli startup with 11.6 Million $ in funding leveraging microbial fermentation to produce dairy proteins.

Biomilk is an Israeli startup developing both lab-cultured cow milk and breastmilk from mammary cells that recently went public.

TurtleTree Labs, a new cellular agriculture startup in Singapore, has taken up the cell-based dairy milk approach. The startup initially plans to produce human breast milk before focusing on other mammalian milk, including dairy milk. Biomilq is a US startup leveraging a breakthrough mammary biotechnology platform to commercialize patent-pending technology to culture human mammary cells to produce custom and commercial lab-grown breastmilk.

Resources:

This fascinating podcast where Raffael, CEO of Formo breaks down the impact of the dairy industry and explains how the fermentation process works.

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