FEATURE: Subtleties in Cells at Work! Episode 6 & 7

So midterm week for summer school was upon me two weeks ago and I had zero time to sit down and catch up with Cells at Work! By the time things started to smooth over, I hopped back onto the internet to realize… that I had missed out on the discussion about cancer.

As someone who recently lost their father to cancer, it’s a very dear topic to me. I joined a cancer research lab, became a bone marrow donor, and practically focused my future interests to figuring out how to eliminate cancer. I vehemently avoided episode 6 and 7, thinking that the show was doing a horrible disservice to those currently undergoing treatment or those who have already passed on. But when I finally sat down to watch it, I became less attached to my feelings toward the show, and I became more intrigued by the multitude of references in every single detail. I ended up gushing over all the references to the AT staff that they ended up encouraging me to do this… analysis of sorts.

By no means do I have as much experience in this field compared to the medical student on reddit or the cancer researcher who applauded the recent episodes via Twitter.  I had taken a physiology class at the same time Cells at Work! first aired at Anime Expo 2018, so this information is relatively fresh in my mind. I also have a STEM background so I do know the bare bones of biology 101. With all this mind, I will do my best to break down some of the more nuanced moments I found within Episode 6 and Episode 7 of Cells at Work!

1.) Is Killer T-cell an actual moron?

NK Cell calling out Killer-T Cell (Source)

There are a lot of jabs between Natural Killer (NK) cell and Killer T-cell, especially in episode 7 where NK cell says Killer T-cell is a moron for not detecting the cancer cell sooner. Based off their character designs and their personalities, Killer T-cell does seem to be the typical Jojo meat-head with no brains, while NK seems to be very cunning and snide. So really, it’s no surprise. But let’s take a look at it from a scientific perspective.

While both killer T-cells and NK cells detect cancer, their methods of approaching cancer cells differs. Killer T-cells, at least in the anime, are usually always late to the scene. This is because in most cases, killer T-cells need to be activated by helper T-cells and various other chemical signals in order to be able to do anything. Additionally, killer T-cells are usually alerted when cells exhibit a pathogenic antigen, a “red flag” that says “I’m the enemy!” and are seen as foreign entities to the human body.

While cancer cells may exhibit antigens, these antigens may not necessarily be pathogenic and present the same antigens as normal cells, thus the killer T-cell is sometimes unable to detect cancerous cells. Some cancer cells can even become resistant to killer T-cells by not displaying any antigens at all, making it even more difficult for killer T-cells to find them. Other times, the number of antigens presented isn’t a strong enough indicator to be noticed by the killer T-cell, or etc.

Meanwhile, NK cells can act independently for the most part. Think of them as the scouts or the spies behind any military force, while the killer T-cells are the ground soldiers. Instead of targeting antigens, NK cells are trained to recognize “self-markers” which normal cells from your own body present. Cancer cells, while originating from the body, somehow lack the “self-marker”. This allows the NK cell to act immediately against cancer cells to try to neutralize the threat.  

However, this is not to say that the killer T-cell is useless. In fact, it’s a massive asset in neutralizing cancer cells due to its cytotoxic properties. But its sensing abilities may not be as sharp as NK cells, as we’ve seen in the anime.

Revived NK-Cell! (Source)

2.) When life gives you neuropeptides, bind to them and laugh!

This is new information to me. I had no idea that by laughing, the brain sends neuropeptides which in turn can “revitalize” NK cells. I ended up opening seven tabs with research papers from the NCBI and three Wikipedia tabs just to fill me in on this phenomenon.

As I read closer into these articles and perused through Google for top hits on NK cells and “laughing”, I didn’t see a lot of underlying evidence. True, there is a correlation between laughing and the release of neuropeptides, but the kind of neuropeptide that is released from the brain varies. There have been a few studies about certain neuropeptides that have a positive effect in bolstering the NK activity, but it’s more so related to inflammation and changes in the body rather than actually laughing. In short, there still seems to be a disconnect between what kind of neuropeptide is exactly secreted when laughing, and if that neuropeptide is directly linked to boosting NK activity.  

However, that’s just to the extent of my limited knowledge. If someone does have actual papers or concrete evidence on the matter, by all means, please link me to the right place! For now, I’ll continue to enjoy the flippant behavior of the NK cell and watch her quickly become my favorite character in the entire series.

3.) Clone yourself so you have more friends!

A key thing to note is that cancer cells do not follow the exact same rules as regular cells. Cells at Work! doesn’t touch up on this as much since that information is a bit unnecessary for the overarching plot of “eliminating the cancer cell”. But we do see the mention of “friend” and “allies” multiple times throughout episode 7, either in the cell’s old room or when the cancer cell is speaking to the White Blood Cell in their last moments. So what’s the purpose behind this reference?

Creepy signs of a mutated cell (Source)

In general, cells cannot replicate whenever they want. Instead, they’re programmed to replicate based on external signals (e.g. chemicals) that can bind to the cell surface and/or according to how many cells surround it. Cells are very sensitive to their surroundings and if too many crowd together in a small area, they’ll stop growing and they will eventually kill themselves because of the lack of nutrients and space, commonly known as density dependency. Additionally, replication can’t even happen unless cells pass the “checkpoints”. These regulations in the cell cycle ensures that the cell’s genes aren’t damaged and the conditions to replicate are favorable.

Cancer cells, however, have no concept of density dependency and will continue to multiply because the checkpoints fail to stop them. Over time, more and more of its “friends” will be produced through replication until a tumor forms, which can then metastasize and eventually spread throughout the body. Furthermore, cancer cells lose the ability to kill themselves off, so there’s literally no stopping cancer cells without the help of the immune system.

The unfortunate beginnings of the Cancer Cell (Source)

4.) Do we really all have cancer cells in us?

Technically, yes. But for those of you who have suddenly become paranoid by this revelation or are extremely uncomfortable because you’ve dealt with cancer before, I need you to take a step back to look at the overall picture.

A normal human body fights against cancer cells every day. By definition, cancer cells are simply cells that have mutated and proliferate without stopping. Several studies over the years have indicated that a good chunk of “common” cancer cells possess an “oncogene”, or a gene that has mutated a certain way and can turn the cell into a cancerous cell in the long run. In the human body already, there are millions of cells that have mutated genes and it’s the immune cells’ job to clean up these mutations, whether they be mutations in the genes causing cancer cells, simple typo mistakes from reading the DNA, or perhaps intentional from the start to ensure the livelihood of the human.

Usually, mutations in cells are taken care of fairly quickly from the very beginning. The immune cells fighting off the mutated cells are like the last line of defense if all checkpoints and correcting measures fail. In extreme cases where the immune system can’t eliminate the cancer cells, then yes, the end product is cancer disease.

5.) Should we feel sympathy for cancer cells?

WBC just doing his job (Source)

This is a hard question. The production team behind Cells at Work! does a fantastic job at tugging your heartstrings by portraying the cancer cell as a “victim” while the immune cells are the “villains” for killing it indiscriminately. Lots of us from the AT team are conflicted, including myself. But this is a usual ploy to invoke sympathy and keep the audience’s attention hooked to the story. This is used in literally every anime, movie, and media you’ve seen, read, or experienced.

The key takeaway from episode 7, I believe, is that no matter what kind of mutations exists in the cells, no matter how small or big the error is, it’s the immune cells’ job to ensure the safety of the body. They work like machines that digest, eliminate, and expel any kind of foreign entity without rest. Without them, how else is the body supposed to adapt to a world that’s constantly full of changes and bacteria or stop the over-proliferation of cells? Give these guys some credit and understand that, yes, it is a cruel job to undertake, but it’s necessary to keep the body alive.  

As White Blood Cell declares at the end of episode 7, “It’s just our job.” And on his behalf, it’s certainly not personal.

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