The Infinite Zenith

Where insights on anime, games and life converge

Tag Archives: Macrophage

On Accuracy in Cells at Work!, and a review and reflection after three

“The premise of the 1966 movie, Fantastic Voyage, involved shrinking individuals to the size of red blood cells to explore the human body, and if possible in reality, journeys of this sort would allow for the complex machinery driving life to be observed at unprecedented resolution and clarity.”

At least, so reads a heavily paraphrased version of my Master’s Thesis paper’s introduction. The Fantastic Voyage was indeed one of the motivations for my thesis project, which involved the recreation of an animal cell within game engine environments such that a user could interact with and explore the different machineries and processes underlying cellular function; this project was intended to visualise cell processes and structures in an immersive manner, and to this end, my visualisations supported both the Oculus Rift headset and the CAVE. Cells at Work! takes the same concept of using memorable visualisations to illustrate processes within the human body, making use of both the manga and anime format to illustrate essential processes within the human body, albeit at a slightly larger scale: to put things in perspective, my thesis would involve showing the cities inside the characters of Cells at Work!. Centered around the adventures of a erythrocyte and neutrophil, Cells at Work! personifies the internal workings of the body to show, step by step, how the body’s internal components operate together in order to facilitate life. So far, the series has covered the response of a body’s innate immune response when S. pneumoniae enter the body, resulting in the use of mucous to trap a remaining pathogen and expel it after the neutrophil-killers deal with the initial invasion. The coagulation response is also detailed: after a surface laceration occurs, the neutrophils appear to contain pathogens while platelets initiate the activation of fibrinogen to fibrin, creating an aggregate to plug the wound while the body delivers the materials needed to patch the damage. In the latest episode, an influenza B infection is presented, with the body activating its Killer T Cells to defeat the virus, which hijacks body machinery to propagate. The primary immune response is shown from the perspective of a naïve T cell, which undergoes activation to help the body defend against the infection. When influenza A appears, however, the body is unable to mount an immediate response. Cells at Work! presents the body as a vast city, and anthropomorphises the constituents to present various process visually, creating an easy-to-remember outline of the body’s processes.

I was given a request to take a look through Cells at Work! and provide commentary on its accuracy from one of my readers. Having looked through the first three episodes, I can say with confidence that Cells at Work! nails the fundamentals. This anime is perfect for showing to middle school students for being able to show complex, and sometimes difficult to visualise processes in a highly accessible and colourful manner. The basics of the biology are correct and give a good overview of how the body’s systems respond to various stimuli: details such as how neutrophils can migrate through narrow gaps between other cells, the fact that erythrocytes must travel single-file through the capillary, and that the immune response has several layers are proper representations of details within the body. However, Cells at Work! also takes a few creative liberties here and there in order to facilitate its story – processes are understandably abstracted out or occur out of order to ensure that the cells’ adventures can still flow from a storytelling standpoint. For example, mucous is one of the body’s first lines of defenses against pathogens, and would be involved ahead of the neutrophils in stopping pathogens. Similarly, the coagulation process is much more complex, involving a tightly-regulated pathway that only allows clotting to occur if the right factors are activated. The generalisation of processes means that Cells at Work! is not likely to be useful as a study guide for secondary biology and beyond. This is not a strike against Cells at Work! in any way, since a detailed anime dealing with protein pathways would also be incredibly dull to watch, and could also be quite tedious to write for (especially considering that not all biological pathways are well-characterised). Overall, the level of detail in Cells at Work! is appropriate for the series, and as it is, this anime is very enjoyable.

Screenshots and Commentary

  • The main erythrocyte is voiced by Kana Hanazawa, of Your Name‘s Yukari Yukino and Shirase Kobuchizawa of A Place Further Than The Universe‘s fame, and a cursory glance at the voices for Cells at Work! show an all-star cast, which is exciting. This post will feature a standard of twenty images, and my answer as to why there are comparatively fewer screenshots despite the biology discussions that I could do, is because the anime is properly enjoyed by watching it.

  • The only thing that readers need to, and should, take away from this post is that Cells at Work! is satisfactorily accurate so that it is a very enjoyable portrayal of what happens within the human body. To put things in perspective, if every protein, cofactor, coenzyme and regulator were to be shown, Cells at Work! would cease to be fun. Similarly, if the anthropomorphic elements were to be made more realistic by depriving them of any personality, there would be less incentive to watch Cells at Work!.

  • As a result, the erythrocyte’s tendency to get lost and the neutrophil’s dramatic combat with pathogens are completely acceptable even though the real body would not work like that: if red blood cells fail to reach their destination, body functions would rapidly decline. Some creative licenses are at play here, but because they’re intended to help facilitate the illustration of certain tasks, and the fact that Cells at Work! presents the interior of the human body as a city with dry air rather than being a water-rich space, some liberties naturally will need to be made.

  • When I began my first summer as an undergraduate researcher at the university, my first project was building a simple model of erythrocyte oxygenation and deoxygenation. This project was to allow me to become familiar with the idea of colliders and trigger zones: my model needed to keep blood cells inside a capillary and oxygenate them at specific spots, then have their oxygen molecules unbind when the cells reached a certain spot to drop off their oxygen. This model was simple and successful, which led me to a more complex project involving flow within complex vessels.

  • The various pathogens of Cells at Work! are depicted as Xenomorph-like monsters that simultaneously resemble villains from series like Dragon Ball Z. Their grotesque appearance is deliberately intended to evoke a sense of disgust in viewers, and the fight scenes, which are bloody, are much more dramatic than how the immune system handles pathogens in reality: white cells will release chemicals to disrupt pathogens or else directly consume them.

  • The use of mucous to impede and expel pathogens is shown as a late-stage response in Cells at Work!‘s first episode, and while the body will actively employ all modes of defense against pathogens, the innate immune system and the physical barriers act as the first line of defense that stop most pathogens from entering the body. Pathogens that do evade these defenses are dealt with by an inflammatory response and white cells.

  • The platelets have rapidly become a fan favourite amongst viewers for their small size and adorable mannerisms, resembling elementary children in appearance. They are voiced by Maria Naganawa, known for her previous work as Miss Kobayashi’s Dragon-Maid‘s Kanna and Slow Start‘s Kamuri Sengoku.

  • Strictly speaking, erythrocytes lack the ability to carry anything other than oxygen and carbon dioxide. Nutrient molecules dissolve directly into plasma and are ferried about the body by blood flow. However, since plasma is absent in Cells at Work!, I will ignore this oversight: it would have been quite strange had Cells at Work! chosen to show nutrients floating around on hover-pads or similar. After an abrasion opens a hole in the skin, the erythrocyte falls into the abyss but is saved when the neutrophil hauls her back up.

  • Regular incidents in the body are depicted as a battle of life and death for the various cells, and while some folks feel this to be done for dramatic effect that increases the entertainment factor in Cells at Work!, I add that Cells at Work! gets the scales of different events correct. What we brush off as small cuts or entry of pathogens as minor, but at the microscopic level, these are massive events. By comparison, consider the collision of a 100 meter-wide asteroid with the planet’s surface. The effects on the ground would be devastating to us, but from the planet’s scale, this is a very minor impact event.

  • Earlier, I mentioned that if Cells at Work! were to depict the molecular processes I show in my thesis work, then the scale differences would be equivalent to zooming in and presenting the erythrocyte’s body as a town of its own. Erythrocytes are 8 μm across, and the haemoglobin protein is 6.5 nm wide. With three orders of magnitude in the size difference, this comparison is not a particularly difficult stretch to imagine, and is one of the reasons why replicating the scales inside the human body using a game engine is so difficult. For my thesis, I ended up using sleights-of-hand to mimic the differences of scale.

  • I mention above that I’ve chosen to paraphrase the opening to my thesis paper: the reason for this is that if the first two sentences are entered into any search engine, the thesis paper itself will be the first thing that comes up. Access to this paper is only available on request, and speaking of requests, this post was done in response to a request from a reader, who had been wondering about how accurate the science driving Cells at Work! is. I hope that the contents here will provide a satisfactory answer for them.

  • After the abrasion is detected, the platelets spring into action and begin patching the hole up. The actual process behind coagulation is much more complex: there is a multi-step pathway where a wound causes platelets to aggregate at the site of an injury, which has exposed collagen. Platelets then bind to the injury site and release agents that recruit more platelets. The coagulation cascade occurs; prothrombin is activated and becomes thrombin, which activates fibrinogen to fibrin. This protein then covers the wound to form a clot. Cells at Work! skips over the involvement of the other factors, instead, showing the platelets as manoeuvring a large fibrin sheet into place.

  • My old cell and molecular biology instructors would probably recoil at the depiction of coagulation in Cells at Work!, as the level of detail shown is no substitute for a physiology textbook at the university level. Abstracting things out, however, makes things quite suited for a general audience, and so as long as one is not wondering about biological pathways, activation factors and regulation, they should have a reasonably easy time enjoying Cells at Work!, which shows the higher-level processes faithfully.

  • A naïve T cell nervously looks around in an area of an influenza infection, which is astutely represented as an undead infestation. This is a clever visualisation, since viruses operate by injecting their DNA or RNA (depending on the virus type) into a host cell and other agents to hijack cellular machinery, forcing the host cell to produce viral proteins. The cell eventually dies and releases nascent viruses which infect other healthy cells.

  • Macrophages in Cells at Work! are voiced by Kikoe Inoue (Belldandy of Ah! My GoddessPlease Teacher‘s Mizuho Kazami and CLANNAD‘s Sanae Furukawa, to name a few). They carry a large billhook into combat with them, which they use to cut down pathogens. This completely defies my expectation of seeing them eat foreign matter. Their name in English is literally “big eater”, derived from Greek (μακρός (makrós) for large, φαγείν (phageín) meaning to eat), and they can extend their cytoplasm to engulf pathogens, before digesting them with enzymes.

  • Killer T cells release cytotoxic compounds when exposed to specific antigens to destroy cells that have been damaged by pathogenic activity or cancer cells. Their interactions are much more complex than Cells at Work! suggest; the process is again, abstracted out. Reading through my old textbooks makes me realise the extent to which I am out of practise with the lower-level details of the immune system: when I saw the dendrictic cells, I began thinking about dendrites of the neurons, rather than the antigen-presenting, accessory cells that are found in tissues contacting the outside environment.

  • So far, all of the processes shown in Cells at Work! after three episodes have been those that my old lab has built in a game engine: my colleagues have constructed an immune response model and a coagulation model in an in-house game engine. As a part of my Master’s thesis, I built a very simple influenza infection visualisation, where viral particles could enter a normal cell and hijack its machinery to produce new virus particles. Because the game engines are very taxing, I set the system to only produce four new viruses. This exercise was intended to show that with generic components, I could adapt my cell visualisation model to illustrate a wide range of processes.

  • I am pleasantly surprised that the number of discussions surrounding the minor inconsistencies in details for Cells at Work! is minimal, with most people speaking of the enjoyment they get from watching this, as it gives them a sense of appreciation for how tirelessly biological processes work. Similarly, folks with a background or even careers in biology have stated that the details are passable and accessible, rather than trying to pick the show apart. By humanising the processes, Cells at Work! aims to convey the complexity of the worlds inside us and just how intricate the building blocks of life are.

  • I am almost certain that my supervisor, who had allowed me to reference The Magic School Bus, Futurama and Rick and Morty in my thesis paper would have no trouble with me including Cells at Work! in my thesis as a part of the motivators. With the sheer complexity and scope of things that go on inside the human body, there is no limit to what Cells at Work! could depict in its run, although I will note that some of the more terrifying or poorly-understood conditions would remain outside the realm of this series to present.

  • Cells at Work! is immensely entertaining, and earns an A grade. I expect it to be consistently enjoyable, with the only real downside being that the anime does not have the likes of Jay Ingram providing a narration. Beyond this, it’s a series that many will find enjoyable; the reason that I would think that this is a difficult series to write for is that I would need to frequently go back into my old textbooks or literature to make sure what I write is correct. This is a time-consuming process, and with the Road to Battlefield V in full swing, I personally feel that I’d rather spend my down time blowing stuff up, rather than reading textbooks well after the last paper, assignment and exams have ended.

I’ve previously stated that I do not like to wave credentials around when it comes to entertainment. This has not changed: in the case of Cells at Work!, the focus on biology means that I am merely applying my background in biology to drive discussion. Specifically, prior to doing a post-graduate degree in computer science, I graduated with a degree in Health Sciences and specialised in Bioinformatics. I spent my undergraduate career studying cell and molecular biology, genetics, proteomics and research methodologies, and my undergraduate thesis was a physiological model of the renal system, so I have a modest familiarity with biological systems at the higher levels. As such, when I read through my old textbooks and literature to gain a better idea of how the systems shown in Cells at Work! work, I can keep an eye on ensuring that what I return to readers is accurate to how things work, while simultaneously making sure that what I say is understandable. I think I’ve done a passable job of this for my first impressions talk on Cells at Work!, and so, when I say that Cells at Work! is accurate enough, readers can take my word for it that the anime will not do anything that is contrary to what is understood about the human body. Cells at Work! brings fun into a complex topic and, like my thesis work and the film Fantastic Voyage before it, makes the world within our bodies accessible to a general audience with a unique flair. I presently have no plans to write about Cells at Work! regularly, but I do recommend it to all viewers (I hardly ever recommend an anime after three episodes, which speaks to the fun factor in Cells at Work!), and I might return once the series has concluded to offer more insights into one of the few anime out there that, like the Giant Walkthrough Brain, is a well-written and enjoyable form of edutainment.