A Comparison between Mammals and Insects for Cellular Agriculture

When it comes to cellular agriculture — the science of creating animal products without the animal — not all animal products are created equal. The resources that have to be invested in the cells, the way they behave and what you can do with them are largely influenced by what kind of organism you are getting your cells from.

At first glance, this might not seem inherently important because cows, pigs, sheep — they’re all quite similar, they’re all mammals. In the western world, we’re accustomed to getting a lot of our protein from mammals and a little bit from fish and birds. And this is why a lot of cellular agriculture startups and companies have revolved around bringing things like beef and pork and chicken to market.

But, what about insects?

This idea is probably pretty foreign to many, but insect cells hold enormous potential for cellular agriculture, mostly because of the differences in their biology to mammalian cells. These differences ultimately allow insect cells to require less “maintenance” to grow, making them a great entry point for cellular agriculture research.

The branch of cellular agriculture that specifically deals with culturing insect tissue is called entomoculture. So, how exactly does entomoculture compare to conventional mammal cultures?

Environmental Tolerance

Overall, insect cells can withstand a much larger range of environmental conditions than mammalian cells.

When mammalian cells are grown in vivo (i.e in the body), they are exposed to fairly hot conditions — about 37 degrees Celcius. In order to mimic these conditions, bioreactors have to be heated which requires more energy, driving up production costs. Insect cells, coming from non warm blooded creatures, can be grown to scale at room temperature.

As mammalian cells digest and metabolize glucose, they produce lactic acid and other byproducts. As they accumulate, they acidify the cell’s environment which leads to inferior growth conditions for the cell. Unless the environment is rebalanced, the cells will not grow as well. The “rebalancing” of the environment is usually done by replacing the entire culture medium — sometime as frequently as every 2–3 days. Needless to say, this wastes nutrients and is expensive.

Insect cells are more tolerant to different pH levels. When insect cell growth was compared at a pH of 5.5, 6.5 and 7.5, not much of a difference was noted. What’s more, insect cells circumvent in part the production of lactate (i.e. they don’t produce as much lactic acid to begin with).

As a result, insect cultures can get away with full media replacements as rarely as 90 days. Now, the other reason media needs to be changed is because of nutrient depletion. However, insect cells don’t deplete added nutrients as quickly as mammalian cells. The first reason is because they consume triglycerides, glucose and proteins at a slower rate suggesting that they have more efficient metabolic pathways. The other reason is that cell cultures are typically contaminated with lipid cells called trophocytes or vitellophages which are precursors to insect egg yolk cells. These cells are a natural source of fat which can be consumed by the other insect cells.

Mammalian cells also require a relatively precise measure of carbon dioxide and oxygen to grow — as such, cultures are usually supplemented with an extra 5% carbon dioxide. Insects can go with out this supplement.

Serum vs. Serum Free Culture Medium

A culture medium is a substance containing all the essential nutrients like carbohydrates, fats, proteins, salts, and vitamins which a cell needs to grow.

As the culture medium diffuses into the cell, the cell will grow, divide and the cell line will “proliferate”.

Culture medium is an instrumental part of cellular agriculture and generating cultured tissue because it’s effectively what allows us to take a relatively small sample of animal stem cells and end up with an enough to constitute an entire cut of meat. These stem cells would then be put into a bioreactor where they are exposed to a whole bunch of environmental cues which encourage them to differentiate into the specialized kinds of cells we get in meat.

Now, in order to proliferate, a cell does not only require essential nutrients and macromolecules. It also needs things called growth factors. When mammalian cells grow in vivo , these growth factors are supplied by the animal’s blood.

In order to replicate this, the culture medium usually consists of a basal mixture supplemented with extra growth factors. The basal medium makes up the bulk of the culture and contains most of the nutrients while the growth factors are added in trace amounts.

So now the question becomes how do we get these growth factors? Since they all exist perfect proportion in an animal’s blood stream, the natural starting point is mixing some mammalian blood into the medium, specifically something called Fetal Bovine Serum or FBS.

FBS is enormously controversial because as it sounds, comes from the blood of a dairy cow fetus. The two issues with this is that it is a) reliant on animals, hence defeating the goal of cellular agriculture and b) expensive because it is so inaccessible.

Additionally, from a scientific perspective, FBS is typically undefined, meaning that it’s chemical composition varies from animal to animal which for research purposes, isn’t desirable.

There is no other substance that we can easily obtain that can singlehandedly provide all these growth factors, so we turn to trying to make them each individually using recombinant protein production. But, at the moment, this too is crazy expensive.

This naturally leads us to one of the biggest challenges facing cellular agriculture: finding the ideal culture medium which is one that is simple, can stimulate proliferation, is unreliant on animals, is accessible and is cheap.

But because of the fact that mammalian cells rely on a complex array of growth factors, finding a culture medium that satisfies all 5 of these criterion is an ongoing challenge.

Insect cells on the other hand, come from insects which are biologically simpler organisms than mammals. They contain a fluid called haemolymph rather than blood and so do not rely on all the same growth factors as mammalian cells.

This in large part allows us to get around the entire balancing act presented by serum. Instead, insect cell medium typically uses a basal medium (such as Eagle’s Medium, Grace’s Insect Medium or Schneider’s Drosophila Medium) which is supplemented with plant based additives.

Some examples of these plant based additives are things like

  • Yeastolate
  • Primatone RL
  • Hydrolysates
  • Pluronic Lipids
  • Peptides

Additionally, due to insect cells’ limited reliance on growth factors in the first place (animal derived or otherwise), mediums are typically simpler in their chemical composition and are cheaper.

Adherent vs. Suspension Cultures

When mammalian muscle cells grow in vivo, a fundamental part of their proliferation relies on their attachment to the Extracellular Matrix (ECM). In order to replicate this relationship, mammalian cells are usually cultured in adherent monolayers — cultures where the cells grow on something else in layers only one cell thick. This necessitates using bioreactors with a lot of surface area which, when scaled up to the industrial level, is infeasible.

The alternative would be using something called microcarriers which are little bits of material that float around in the culture medium which the cells can attach to, just increasing the overall available surface area. But this requires additional resources and more time to separate out from the meat at the end, complicating the process.

This also introduces the need to vascularize. When mammalian cells are grown in adherent cultures, the cells which are not in direct contact with culture medium will stop growing because they can’t access nutrients. So, the culture medium has to somehow be routed through the meat.

Unlike mammalian cells, insect cells are also able to grow unattached to anything — or in suspension cultures. This means that bioreactors don’t have to have a large surface area, and can instead be produced in much more practical shapes.

So, in summary, the three main ways in which insect cells differ from (and are superior to) mammalian cells are

  1. Higher environmental tolerance, in particular for pH, temperature and gas levels.
  2. The ability to grow in serum free media.
  3. The ability to grown in suspension cultures.

On the other hand, entomoculture is at a disadvantage to mammalian cultures in that the idea of eating mammals is already much more widely accepted in the western world than eating insects. The concept of cellular agriculture in general is not exactly something people are overwhelmingly comfortable with, and so for many, compounding that with insect meat might just make it that much more unappealing.

And of course, although insect cells might be advantageous from a scientific perspective, it doesn’t mean that the only cultured meat we will ever consume will be derived from insect cells. It just means that because of it’s comparatively low maintenance, entomoculture might be a promising area to focus research.

Activator at The Knowledge Society | A Sandwich or Two Founder

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