Cut the BS: Alternatives to Fetal Bovine Serum for Cellular Agriculture

Cellular agriculture — the science fiction fantasy of growing meat in a petri dish — aims to produce animal products without the animal. This field has the potential to revolutionize the way we eat by making food production better for the environment and better for our health.

Gone will be the days of desolate calves chain to posts in factory farms and anxious chickens crammed into battery cages. Gone will be the days of a staggering 14% of our total greenhouse gas emissions coming from fulfilling our basic necessity to eat.

Amazing, right?

Only, there’s one big problem: at the moment, cellular agriculture — ironically — relies on animals. And by “relies”, I mean is almost vitaly dependent.

What, how?

Well, because of a little something called FBS.

Fetal Bovine Serum (FBS) plays a crucial role in culturing meat in vitro — i.e. cellular agriculture.

First, a quick review. Cells are (generally) cultured in three main steps.

1. Stem Cells (cells which have the potential to become any type of specialized cell) are extracted from the animal.
2. They are immersed in a culture medium — basically a large power smoothie — which gives the cells all the essential nutrients, carbohydrates, proteins and fats they need to grow and multiply.
3. They are put in a bioreactor which exercises and introduces the cells to growth factors and encourages them to differentiate into many different kinds of specialized cells.

FBS comes in at step 2. It is what’s known as a serum — it is added to the culture medium, and is what provides all the important nutrients. It is mainly because of FBS that we can start off with a small group of cells and end up with a whole burger, for instance.

Although producers usually refer to it as a “by-product of the dairy industry”, FBS is literally the blood of a cow fetus which is extracted from the womb of a dairy cow when she is being slaughtered. As the fetus is given no anesthetics prior to this process, it will undergo a painful death lasting up to 5 minutes.

Needless to say FBS has significant ethical issues both because of the gruesome way in which it is acquired, and also because it contradicts the goal of cellular agriculture — to produce animal products in such a way to be unreliant on animals.

What’s more, due to its rarity, producers are able to demand a high price for it. In the past few years, it’s price has increased by over 300%. It currently costs up to $1000 per liter of FBS, which easily contributes to the $50,000 cost of culturing one pound of meat in vitro!

Clearly, in order to make this technology cost effective and realize it’s ethical potential, we will need to develop a culture medium that is either unreliant on FBS or uses an alternative.

Research into Fetal Bovine Serum alternatives started in the 1990s, but was not successful enough to attract serious consideration. In 2017, Researchers at Taipei Medical University in Taiwan conducted a study into FBS alternatives in which they compared the effectiveness of FBS and six FBS alternatives on six sets of head and neck cells.

The head and neck cells lines that were used are called NPC-TW01, HONE-1, OECM-1, FaDu, SCC25 and DOK.

The culture serums that were compared to FBS were newborn calf serum (NBCS), bovine calf serum (CS), iron supplemented calf serum (ISC), fetalgro (FG), cosmic calf serum (CCS) and fetalclone III serum (FC3).

A selection of each of these cells was immersed in each type of culture serum and various statistics including

• Proliferation — cell growth and division
• Cell invasion — the ability of a cell to penetrate other tissues
• Cytotoxicity — the ability of a healthy cell to be killed
• Plating efficiency — the number of “colonies” originating from one cell
• Expression of transcription factors — proteins that bind to a cell’s DNA
• Anchorage independent growth — the ability of a cell to grow unattached to anything else

was recorded over different passage numbers (i.e. the number of times the culture serum was refreshed).

Proliferation ratios for each cell line in each culture medium across 4 passage numbers.

Overall, scientists concluded that the FC3, CCS and FG culture mediums promoted equivalent or higher growth than FBS.

They also saw that these three serums mimic some of the helpful characteristics of FBS — most notably cell cytotoxicity and plating efficiency.

Cell cytotoxicity for three different cell lines in four different culture mediums was measured after being treated with different concentrations of cisplatin (a cancer fighting drug).

Plating efficiencies of five cell lines for FBS and five alternatives was measured in the number of colonies the average cell produced.

Now, most of these alternative culture mediums may not seem a whole lot different than FBS — they are all derived from the blood of cows at different points in their lives. However, they differ from FBS in that they are continuous sources, they can be obtained at a reduced price, and do not necessarily require painful treatment to the animal — which were some of the biggest challenges with FBS

In some ways, they are even superior. FBS is typically undefined — scientists can not quantify its specific chemical composition and so it can vary greatly depending on the animal. These proposed alternatives can be quantified exactly which will help scientists to better predict the health of their cell lines.

However, this is by no means and end result — it is only the begining of (potentially very long) path to find a permanent alternative for FBS.

Ideally, such a source would be plant based and hence unreliant on animals, renewable and easily accessible, relatively cheap and rich in nutrients. JUST — a startup which aims to bring cellular agriculture based eggs to consumers — is using AI on a plant database to find a plant which could create suitable growth medium.

Key Takeaways

1. Fetal Bovine Serum (FBS) plays a crucial role in culturing cells in vitro. Due to it’s abundance of nutrients, it is productive in helping cells to proliferate. However, because of the unethical way it is sourced, it’s scarcity, high cost, and variable chemical composition it is not an ideal growth serum.
2. Fetalgrow, Fetalclone III serum and Cosmic calf serum are promising alternatives to FBS in terms of their effectiveness and precision, but because they are also sourced from cattle, they are not an end result.
3. JUST is using AI on a plant data base in hopes of finding a plant which could be a suitable alternative to FBS.