6 min read

Frontier Snippets: Launching a Solo Podcast

Hi everyone,

I'm experimenting with something new. I'm launching a solo podcast series (5-15min long) where I'll cover a series of topics alternating between FrontierTech and Deutschian Philosophy.

On the podcasts covering tech, I'll briefly explain the technology at a high level, cover the challenges and discuss the next wave of innovation in the space. Today's topic is one of my favourites: Cellular Agriculture or sometimes called Cell Culturing.

You can also read it as a Twitter thread here or follow the transcript below:

David Deutsch in his book articulates how humans leverage explanatory knowledge to transform resources and adjust the environment around us to meet our needs. Technologies like construction and agriculture have enabled us to thrive and evolve. But our enormous progress has come at a cost. Conventional agriculture, for example, is a leading contributor to deforestation, climate change, animal cruelty and the spread of infectious diseases.

With knowledge comes solutions, and cellular agriculture claims to offer an alternate solution to growing food and fabrics in a sustainable fashion.

What is cellular agriculture?

Cellular agriculture or cell culturing technique is the removal of cells from a mammal or plant and growing them subsequently in an artificial environment. Cell culturing technique has been widely used in the pharma industry such as vaccine research, cancer research and protein therapeutics(Eg: antibodies, Polio)

In the drug and vaccine development process, cell culturing offers the artificial environment to test compounds and find out how active they are in terms of pharmacological actions. Cell culturing has been used in protein therapeutics where both non-mammalian expression systems (bacterial, yeast, plant and insect) and mammalian expression systems (including human cell lines) have been used to produce proteins.

How does it work?

Cell Sourcing:

Cells can be sourced in three ways:

directly from an organism;

from an already established cell line or

from a genetically modified cell line

Cell Line Development:
The next step is the discovery and development of single cell-derived clones that produce high and consistent levels of desired genes. Normal cells usually divide only a limited number of times before losing their ability to proliferate. However, some cell lines become immortal which can occur naturally or induced chemically or virally.

The cells are then made to proliferate in stages under the appropriate conditions in a medium.

Mammalian cell culture media contains a balance of pH, salts, carbohydrates, amino acids, vitamins, fatty acids, lipids, growth factors, hormones, trace elements(amino acids, sugar, carbohydrates, vitamins, minerals: Copper (Cu), iron (Fe), manganese (Mn), molybdenum, nickel (Ni), selenium (Se), silicon (Si), zinc (Zn), and others), and serum.  Hormones promote cell growth and can act in a cell-type-specific manner. Some cells require hormone supplements to grow under in vitro culture.

Cell Proliferation:

Once the cells occupy the initial media, they are subcultured by transferring to a new culture medium like a bioreactor where they can continue to grow. From sizes as small as 50 litres to 20,000 litres.

A bioreactor like any system has inputs and outputs. The inputs are usually energy sources that help the cells to proliferate. These include growth factors (basically proteins), essential nutrients, hormones, Gases (O2, CO2), a regulated Physico-chemical environment (pH, osmotic pressure, temperature).

Glucose is the most commonly added sugar in the cell culture process and is an indispensable substance as the main energy source of cells in the culture medium. Alternatively other sugars: fructose, oligosaccharides, etc as a carbon source

The outputs are usually components for withdrawal of cells/medium, excreting waste or collecting water for reusing.

A bioreactor essentially has 5 main functions:

  1. Agitation (for mixing of cells and medium),
  2. Aeration (aerobic fermentors); for O2 supply,
  3. Regulation of factors like temperature, pH, pressure, aeration, nutrient feeding, and liquid leveled.
  4. Sterilization and maintenance of sterility, and
  5. Withdrawal of cells/medium

Current cellular agriculture methods have two stages in the bioreactor pipeline:

The initial cell culturing is done in large fed-batch bioreactors that are 15,000 to 20,000 litres in size. Cells are cultured in batches that last between 1-3 weeks when all media nutrients are consumed and waste collected. They are then transferred to perfusion bioreactors where the cells mature, differentiate and are further processed into food. Culturing in perfusion bioreactors last for months where the cells are continuously fed with fresh media while spent media is removed.

Challenges:

Meat is the first non-pharmaceutical product that was created via cell-culturing

Cultured meat was first introduced in 2013. The biggest challenge is not the product but scalability and achieving pricing parity . The first cultured beef was sold at 330,000 USD.

The article 'Lab grown in meat is supposed to be inevitable. The Science tells a different story.' is an interesting read. Although it sheds a pessimistic light, some of the key challenges described the author seem to be valid.

  1. Scalability

Producing something at small scale in biotech is relatively straightforward. However, as processes are scaled, the expenses start to go up as bioreactors of increasing volume need to be created.  Bigger bioreactors also struggle to provide all of the cells with the same amount of nutrients and oxygen. With each level of progression in size, the need for re-optimization of various parameters such as unit operations, fluid dynamics, mass transfer, and reaction kinetics come with increasing complexity and cost.

2.  Serum

A key ingredient of cell culturing technology has been serum, a component of blood, for growing and maintaining cells in culture. It contains a mixture of proteins, hormones, minerals and other growth factors. It is added to media as a growth supplement as it supplies cells with nutrients and stimulates growth factors. Conventionally, fetal bovine serum (FBS), a blood product extracted from fetal calves has been used but is unsustainable and resource-heavy to produce. there are also large batch-to-batch variations. In addition, the use of a component directly sourced from animals, albeit it being considered waste from abattoirs, has been a controversial topic of discussion. Cultured meat companies have been putting significant resources into alternative growth media.

3. Scaffold Structure:

Scaffolds provide structure for cells to form tissues that are larger than 100 µm across. The choice of material for a scaffold should be non-toxic for the cells, edible, and allow for the flow of nutrients and oxygen. On the other hand, they should also be inexpensive and easy to produce.

4. Clean room/sterility:
Sterility is defined as the inability of an organism to reproduce. Mammalian cells are vulnerable to the presence of bacteria and virus that may contaminate the cell culturing process and induce sterility. Therefore, the need to maintain clean rooms becomes extremely important. The introduction of even a small speck of bacteria or virus could mean the whole plant needs to be shut or taken apart and reconstructed.

Although the counter article focuses on techno-economic analyses based on current technologies to claim cell culturing will not yield the necessary volume or achieve the price parity, it fails to include the most important factor: Radical innovation that is happening behind closed doors and the ones that are yet to come.

For example, there is already a 2nd wave of startups and research groups aiming to supply into the cultured meat market. From improved cell-line development to new modular bioreactor designs and from optimizing media composition to solving texture for cultured meat.

In a rebuttal to The Counter article, Good Food Institute points out, a key paradigm shift between cultivated meat and nearly all prior applications of animal cell culture technology is that here, the cells themselves are the product, rather than using the cells as manufacturing factories for some other high-value product.

Additionally, as mentioned earlier, meat industry isn't the only industry focused on cell culturing solutions, companies are working toward culturing chocolate, leather, cotton, milk, etc. It is in fact possible that parallel innovations across different industries will make technologies associated with cellular agriculture affordable and scalable.

The cellular agriculture industry is still at infancy, yet there are more than 80 cultivated meat companies with billions of dollars of VC backed money. The industry still needs more capital and we need more investments, particulary from the governments, to solve the grand challenge.

It is highly likely that cultured meat will not compete directly with commodity meat any time soon but rather focus on the market driven by conscious consumer interests. Having said that, the prices of commodity meat won’t stay cheap: It is already starting to increase. With an increase in the global population and more families expected to move from low income to high income economy over the next decade, feeding more people implies more animals in less land. This increases both demand and the chances of diseases spreading which will affect the price of commodity meat.

Technological progress isn't inevitable, it can be achieved only through innovation, creativity capital and consumer demand.

You could support my work by purchasing a database of FrontierTech startups across different industries that may be of interest to you on Gumroad.

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