FBS — The Ethical Dilemma you Probably Didn’t Know is Happening

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Visionary Hub

10 min readJul 20, 2022

Should animals be used to test medical products?

This is a debate that researchers and scientists alike are constantly confronted with. On the one hand, these animals can feel pain and aren’t perfect replicas of our anatomy as humans. On the other hand, the models of some animals (ex. mice 🐭 and monkeys 🐵) are close enough to people and allow us to develop effective treatments (ex. antibiotics, insulin, vaccines 💉) against many diseases.

This debate, like many others, doesn’t have a correct answer. However, a compromise has been reached in form of the 3Rs: reduce, refine, and replace. The 3Rs act as principles that researchers follow to lessen the harm done to animals.

Examples of each category of the 3Rs. Image credit: Science

For now, let’s focus on ‘replace’. The figure above states that an example of the replace principle is cultured cells. Cultured cells are grown in vitro (outside a living organism, inside a dish or test tube) by humans. Scientists can modify these cells to carry out their experiments.

On paper, this sounds like a great solution to our ethical problem. We don’t need to physically harm the animals when we can make cells!

Well, let’s dive a bit deeper. These cultured cells need a culture medium from which they can reproduce. So what’s the main medium being used today?

FBS, also known as Fetal Bovine Serum 🐮.

If that name didn’t already raise some red flags, FBS is a byproduct of the meat industry. When pregnant cows are slaughtered, blood is extracted from the embryo (the unborn calf). The liquid that remains is used for FBS.

Cows in the meat industry are often raised in an environment like this. Image credit: The Humane League

It seems the word replace is a bit misleading. But how can we fix this? Should we fix it? All these questions (and more!) will be answered in this article.

Psst… if you’re feeling lazy, scroll to the bottom for a TL;DR section!

Why is FBS Widely Used?

There are a variety of reasons that FBS is the number one culture medium. To make this easier to digest, I’ll be dividing this section into two subsections: scientific and economic.

Scientific

FBS is typically used in only 2–10% of the culture medium, though this number varies based on what kind of cells are being cultured. But this portion contains many vital growth factors, such as hormones, nutrients, and sugar. FBS also contains fewer growth-inhibiting factors (such as y-globulin), furthering the growth rate of cultured cells.

Table showing the chemical composition of FBS. Image credit: ResearchGate

To understand that concept better, let’s say you’re a zookeeper looking after the newly arrived tiger cubs 🐯. Their habitat is a very controlled environment with a decent amount of space. But there’s one thing missing: food. To ensure the cubs grow up to be nice and strong, you set up a corner of the habitat that would be filled with meat. The meat “buffet” doesn’t take up much space, but it still contained crucial proteins needed to ensure the cubs can grow up efficiently and safely.

The meat buffet represents FBS — there may not be much of it, but it’s enough to boost that growth rate and sustain the cubs (or the cells).

Moving along, another benefit of FBS has to do with its protected origins. FBS is taken from pregnant cows so the embryo doesn’t have any exposure to potentially harmful bacteria from the outside world.

Finally, FBS functions with numerous types of cells, making it more desirable for many experiments.

Economic

The bulk of the benefits of FBS lie within the scientific section, but there are still a couple of benefits on the economic side of things.

As I mentioned before, FBS is a byproduct of the meat industry. This makes FBS quite easy to produce. As long as you have pregnant livestock, you can get yourself some FBS. It’s also an effective way to make a quick buck 🤑. Not only are you manufacturing your meat products, but you’re also selling the leftovers — a win-win situation.

Diagram that illustrates the production cycle of FBS. Image credit: European Serum Products Association (ESPA)

There is also a high demand for more FBS as we conduct more experiments, which encourages more livestock farmers to sell their cattle’s blood.

What’s Wrong with FBS?

Once again, this section will be divided into subsections, but this time we will explore three categories: scientific, economic, and ethical.

Scientific

One of the most notable problems with using FBS is the batch-to-batch variations. If there’s one thing science class taught me, it’s to keep control variables well controlled. This increases the likelihood of similar results in others’ experiments and the reliability of your experiments.

FBS batches vary in quality, both seasonally and geographically 🌎. Typically, FBS produced during winter ❄️ and spring 🌸 is less effective at promoting cell growth. At the same time, FBS coming from various locations could experience different kinds of contamination.

Diagram showing variations between several batches of FBS. Image credit: ResearchGate

Additionally, FBS can interfere with cell stability. This could mean causing stable cells (cells that grow at a normal rate) to grow more or less than needed. Although having the cells reproduce quickly is part of the reason why FBS is so desirable, cells that multiply too fast could end up with genetic 🧬 mutations. This would go on to cause many problems within the cell line.

Due to the lack of certain proteins in FBS, there is also a chance for vascular and chronic inflammation. There is also the possibility that the usage of FBS could manipulate the progression of tumors.

Finally, there’s still a lot we don’t know about the composition of FBS. Using FBS now is like if you programmed a robot 🤖 to do your dishes… except you have no idea how you did it. Yes, it does clear up more room for Netflix in your nightly routine, but you couldn’t debug your robot if something went haywire. The same applies to FBS — since we don’t know how it works, we can’t easily understand issues that may arise. We may not even realize these issues exist.

Economical

Remember how I mentioned that the high demand for FBS resulted in a better economic situation for livestock farmers?

Well, that’s where the economic benefit ends.

The increased demand for FBS has caused prices to skyrocket by over 300% 💸! In the long run, this harms the economy because we have to pay more for these items, leaving us with less money. TL;DR — we lose our purchasing power.

The current future of the FBS market — 2028 isn’t that far off! Image credit: Adroit Market Research

The price isn’t the only unstable force for FBS — the availability can be just as wild. The availability of FBS relies on many factors such as the weather, the amount of livestock, and the price of produce.

There’s also a situation with the marketplace. Since there aren’t many rules and regulations in the said marketplace, exploitations of FBS aren’t a rare occurrence.

Ethical

Finally, we get to the ethical issues. You may have noticed that I didn’t include ‘ethical’ as a category when discussing the benefits of FBS. That’s mainly because my research couldn’t find any evidence to support that argument. When discussing FBS, there is a lot of proof to back the negative outlook.

For any debaters reading this, your mind may jump to one place first: can an unborn cow feel pain?

After that question, you may think of another question: what is pain?

According to the Merriam-Webster Dictionary, pain is “a localized or generalized unpleasant bodily sensation or complex of sensations that causes mild to severe physical discomfort and emotional distress and typically results from bodily disorder (such as injury or disease)”

Now, sensations require a conscious where they can signal discomfort. This conscious is none other than the brain 🧠. So, do cow fetuses have brains?

Bovine fetuses begin developing neurological pathways (including the brain) throughout the third trimester of gestation, the time when the calf is still developing in its mother’s womb.

All of this proves that an unborn calf can feel pain. So when blood is extracted from the embryos, the calf suffers from anoxia, the absence of oxygen. This would likely cause some discomfort, especially as it takes 15–20 minutes before the calves succumb to anoxia.

Some precautions are taken when the fetus is removed from the cow. If it comes into contact with the air, it becomes conscious. And as I mentioned before, with consciousness comes sensations of discomfort. Therefore, they are taken to a separate room, at the absolute maximum, 40 minutes after slaughter.

There’s an argument to be made that the fetus is handled with delicacy and care to prevent harm and that the fetus would die anyway. However, the fetus still feels pain and it feels immoral to be killing unborn cows. Around the world, the number of killed bovine fetuses is growing, like some sort of sick video game where the person with the most kills wins.

There has to be another way… right?

What is the Best Alternative to FBS?

To answer that question, we have to lay out some criteria. The ideal FBS replacement should:

Have consistent batches and availability
Increase and assist the growth of cultured cells
Be compatible with a variety of cells
Reduce or avoid harm to living organisms

I’ll be comparing bovine ocular fluid, fish 🐟 serum, sericin protein, human platelet lysate (HPL), and earthworm heat inactivated coelomic fluid (HI-CF).

Bovine Ocular Fluid

Bovine ocular fluid, like FBS, is a byproduct of the meat industry. It’s gathered from the eye 👁 of a slaughtered cow. Since the cow is already dead when the fluid is collected, bovine ocular fluid is already a step ahead of FBS.

Bovine ocular fluid contains the same desirable growth factors that FBS has. It can also speed growth rates and help the growth of WISH (Wistar Institute Human Amniotic Cells), Human Bone Marrow Fibroblasts, and Vero cells (Vervet Monkey Kidney) better than FBS can.

Unfortunately, there isn’t enough bovine ocular fluid to meet the demand that FBS created.

Fish Serum

Fish serum, as you might guess, comes from fish and is a byproduct of the fish industry. Like FBS, this allows fishers to a) produce fish serum with ease and b) earn some extra money💰.

But fish serum has one big issue that contradicts the criteria — it isn’t consistent. Fish serum suffers from varying batches, which pretty much makes it ineligible as a replacement for FBS.

Sericin Protein

Sericin protein is a byproduct, not of the meat industry, but silk harvested from a silkmoth’s cocoon. This protein naturally increases cell proliferation due to certain amino acids.

Sericin protein has promoted both the growth of mouse fibroblasts and cell attachment in human skin fibroblasts. Additionally, many different human cells have been cultured using sericin protein. These cells include HeLa cells, T-lymphocytes, human marrow stromal cells, and more. However, in CHO (Chinese hamster 🐹 ovary) cells, FBS and sericin protein are virtually the same.

HPL

Since the role of platlets in the body is to clot up open wounds, it’s safe to say that they would be good at increasing cellular growth rates. HPL has many different growth factors, including the platelet-derived growth factor. All the growth factors in HPL rapidly boost cell growth and proliferation.

Another benefit to HPL is its versatility. Some cells may require different methods for them to be cultured. HPL can support multiple of these techniques.

HPL is also highly accessible thanks to blood banks🩸 around the world. The only harm being done to a living organism is a little prick! And that’s not all. Because of how protected the environment is at blood banks, HPL is ideal for a clinical setting. where it can be used to research immunotherapies and regenerative medicine. HPL can be used to culture primary human macrophages!

Earthworm HI-CF

The coelomic fluid (or CF)’s function in an earthworm🪱 is to transport immune cells to where they need to go. Interestingly enough, this fluid’s composition is rather similar to a serum. For example, both contain plasma. CF also has important hormones and growth factors that are beneficial to a culture medium. The CF of certain earthworm species even adds a boost to their cell proliferation!

However, plain old CF can be toxic. This is why it’s heat-inactivated!

HeLa cells and mouse primary fibroblast cells were successfully cultured using HI-CF from a P. excavatus earthworm. They grew well and were more viable when compared to FBS. There were also not any cellular or morphic changes when using earthworm HI-CF instead of FBS.

Earthworm HI-CF does have one problem though — it struggles to initially attach to the cells, decreasing efficiency.

Step-by-step for HPL and HI-CF usage. Image credit: ScienceDirect

Verdict

Out of the options listed above, HPL and earthworm HI-CF are the strongest options 💪. Both excel at raising cells, either equal to or better than FBS. They are also easily accessible and easy to produce. As the cherry on top, neither HPL nor earthworm HI-CF raise any ethical concerns.

A potential future could see a combination of these two alternatives to make them even more effective. The mixture of their growth factors could continue to up the growth rates. To make this future a reality, more research needs to be done to ensure nothing goes awry.

TL;DR

FBS (fetal bovine serum) is a byproduct of the meat industry, created from the fluid within the embryos of a slaughtered pregnant cow. It is commonly used as a culture medium due to its abundance of growth factors
It turns out FBS is a weak culture medium — there are consistency problems in the scientific realm, unpredictable prices in the economic realm, and many ethical problems
Some potential alternatives to FBS are bovine ocular fluid, fish serum, sericin protein, human platelet lysate (HPL), and earthworm heat inactivated coelomic fluid (HI-CF)
The strongest alternatives are HPL and earthworm HI-CF, potentially a combo of the two. However, more research must be done before this is achieved