The Cell Cycle: Mitogen

The Cell Cycle investigates the mechanisms and substances that regulate cell division and growth. The process of deciding to divide, or not, is a highly regulated interplay of messages and receptors reporting on the state of the environment and the state of the cell. While contemporary conditions have prompted most animal species to initiate an evolutionary process of shrinkage, humans continue to grow taller. Twenty-first century Homo sapiens is the tallest human species of all time. Our contemporary cell climate is one of constant high biological and cultural pressure to proliferate, to expand, divide and grow bigger. It is a situation of biological confusion because of an ill-informed and misdirected cultural environment. The global human body is manipulated into expressing growth as the best strategy for longterm survival while in fact shrinking would be the more rational and sustainable choice.

The divisive processes within the cell cycle that express this confused situation are initiated by mitogens, the signals involved in giving the green light to go ahead at a critical point in the cell cycle. A mitogen is an intermediate agent between the cell and its environment that encourages, if conditions seem favourable, to commence cell division. Mitogens act primarily by influencing a set of proteins which are involved in the restriction of progression through the cell cycle, especially checkpoint G1. Before clearing the checkpoint in G1 the cell can still abort the process of division. After G1 is passed growth abortion becomes much more complicated as the cell is able to continue autonomously without the need for external signals. If mitogens are over-expressed they may cause growth that is unnecessary or even damaging, like in cancer as well as the irrational increase in human height. Both symptoms are defined by a lack of, or failure of, control in the cell cycle. Mitogens can cause the cell cycle to move forward when in fact it shouldn’t. In normal cells this would be corrected by mechanisms designed to prevent the uncontrolled growth of cells, internal or external. Current signalling in and around the cell has allowed the human species to grow to an unprecedented size that poorly reflects global environmental conditions. Pressure on our resources has never been greater. Unless we study mitogen from the position of a desire of non-proliferation we will never understand how global height can be decreased.

Calimero Complex

In the Low Countries the Calimero Complex refers to people, organisations or countries that feel they’re under-appreciated because of their small size. The name given to the complex refers to the lead character Calimero in an Italian animated cartoon series featured in the early 70’s on Dutch and Belgian public tv. Calimero is a small black chick in a family of only yellow chicks. He wears half of his egg shell still on his head. His small size often makes him cry out: “They are big and I is small, and that’s not fair, oh no!”. Rather than the Napoleon Complex or other forms of supposed low self-esteem because of size, the Calimero Complex is understood to be a more passive state of feeling sorry for oneself while at the same time blaming others for your own shortcomings. It’s a presumptuous definition, to say the least.

The Dutch are the tallest people in the world. It is therefor interesting to note that the use of the term Calimero Complex is used exclusively in the Low Countries. After all it is easier to make such size-related judgements of a specific type of behaviour or character from the perspective of (mistaken) presumed superiority. Saying somebody has a Calimero Complex says just as much, or more, about the supposedly privileged person saying it.


What does it mean when your spelling control keeps changing the word degrowth into the word regrowth? How obsessed with growth must a society be when decades after the word degrowth was introduced to inspire a paradigm shift towards the destructive idea of continuous economic growth, our vocabulary still does not except it, and not only presumes it to be a mistake but suggests us to embrace the correct ideology of regrowth? Are our ‘intelligent’ economy-bound algorithms not allowing us to think in terms other than more?

Hallmarks of Malignant Growth: Tumor-promoting Inflammation

In trying to understand what makes the idea of continuous growth so powerful (despite clear evidence that it is a harmful concept) The Incredible Shrinking Man turned to cancer research to learn where healthy growth turns malignant. Although cancer is a very complex phenomenon the seminal paper “ The hallmarks of cancer” managed to simplify its underlying process to ten common traits that every single cancer shares to facilitate the transformation from a normal cell to a cancer cell. Published by Robert Weinberg and Douglas Hanahan in 2000, with an updated version in 2013, the paper functions as a guide and lens to learn what the underlying principles of growth are. And what to do about it when things go wrong. Like in our growth-obsessed economy perhaps.

The eighth hallmark of cancer is that it can corrupt and recruit the immune system to help it survive, grow, migrate and start colonies. This process is enabled in a climate of constant inflammation. Normally, inflammation is how tissue responds to injury, for instance during the healing of a wound. It is local and protective. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair. However, if the inflammation-causing agent persists for a prolonged period of time, the body’s response to it becomes a chronic inflammation, which increases cancer risk. There are many similarities between a cancerous tumor and a healing wound. The ‘healing’ processes are controlled by growth factors and signaling molecules. The inflammatory response, which involves the activation of the NF-beta-B pathway, activates a wide range of genes involved with providing exactly what cancer needs to survive, grow and migrate. Just as the immune cells gather near a site of injury to secrete growth factors to begin tissue repair, tumors can also surround themselves with immune cells that secrete these same growth factors to promote their uncontrolled cell growth. Various types of immune cells are involved but the main culprits are known as Tumor Associated Macrophages (TAMs). In some instances they comprise as much as 50% of the tumor mass. TAM’s assist cancer cells in bypassing some of the anti-cancer defense mechanisms as described in previous posts: 1. They secrete and provide growth factors to the tumor. 2. They promote angiogenesis by secreting VEGF and PDGF in the oxygen deprived regions of the tumor. 3. They suppress the adaptive immune system by secreting immunosuppressive molecules, or by attracting other inactive immune cells. 4. They degrade the extra cellular matrix by expressing the enzym metalloproteases, thus allowing for metastasis.

Amplexus Tantra

It may seem farfetched and even a little awkward to discuss a frog’s preferred sexual position as part of a strategy to shrink. However, to change humanity’s irrational desire for bigger towards a much wiser desire for smaller we must invest as much in alternative fantasies and imaginative storytelling as in the instantly practical.

In the light of the dominant universal female preference for taller males, the dominant amplexus technique seen in frogs, toads, newts and horse crabs opens up a window of tantric opportunity. During amplexus, the female carries the male around on her back. To make sure he doesn’t fall off different species of frogs have different preferred places to hold onto. Sometimes it is the back, sometimes the legs and in some cases the head. All this hanging around may not seem particularly friendly towards the female frog, and perhaps it wouldn’t be if it were not for her preference for small males. The smaller the male, the more stamina and the more pleasant it is for the female to perform her side of the act. Which is all the better since the whole thing can last many hours.

But most importantly,  the smaller the male the smaller the offspring.

Micro-Livestock’s Short Shadow

Livestock’s Long Shadow: Environmental Issues and Options, a 2006 report released by the Food and Agriculture Organisation, assesses the impact of the livestock sector on environmental challenges, along with potential technical and policy approaches to mitigation. The livestock sector poses serious challenges to the environment at every scale from local to global. According to senior U.N. Food and Agriculture Organization official Dr. Henning Steinfeld the meat industry is “one of the most significant contributors to today’s most serious environmental problems” and “urgent action is required to remedy the situation.” The report evaluates that livestock are responsible for 1/5th of global greenhouse gas emissions, arising from feed production, fertilizer production, deforestation, feed and animal products transport, soil erosion in pastures and feed crops, enteric fermentation and methane and nitrous oxide emissions from manure. If man shrinks his needs shrink. Physically downsizing existing livestock or moving towards smaller alternative livestock options will have significant consequences in battling meat’s negative contribution to environmental challenges.

Hallmarks of Malignant Growth: Genome Instability and Mutation

In trying to understand what makes the idea of continuous growth so powerful (despite clear evidence that it is a harmful concept) The Incredible Shrinking Man turned to cancer research to learn where healthy growth turns malignant. Although cancer is a very complex phenomenon the seminal paper “ The hallmarks of cancer” managed to simplify its underlying process to ten common traits that every single cancer shares to facilitate the transformation from a normal cell to a cancer cell. Published by Robert Weinberg and Douglas Hanahan in 2000, with an updated version in 2013, the paper functions as a guide and lens to learn what the underlying principles of growth are. And what to do about it when things go wrong. Like in our growth-obsessed economy perhaps.

The seventh hallmark of cancer is its ability to outcompete surrounding cells through a succession of alterations (mutations) in its genome. If a mutation enables faster growth or a longer life span, and has more offspring, then that cell has a selective advantage. Tumor progression can be portrayed as a succession of clonal expansions, each of which is triggered by the chance acquisition of an enabling mutant genotype. There’s an increase in mutations as the genome surveillance system is compromised while the accumulation of  a cancer’s ‘capabilities’ makes it more and more aggressive and dominant over its surroundings. The cancer evolves to evade attack by immune cells, escape the apoptotic machinery which causes cells to self-destruct, corrupt and co-opt otherwise loyal surrounding cells and migrate to distant parts of the body. With an average (one hundred million billion) cell divisions during a life time even the very small chance of mutation still makes the probability of a mutation occurring in a gene high. That’s why the DNA repair mechanism is so important. The DNA repair ability of a cell is vital to the integrity of its genome and thus to the normal functionality of that organism. Many genes that were initially shown to influence life span have turned out to be involved in DNA damage repair and protection. Two of the best known molecular caretakers of this process are BRCA1 and BRCA2. When there’s a mistake during duplication BRCA moves to the damaged site and starts the repair process. Cells with flawed or missing BRCA are very sensitive for mutations. In addition to being crucial for DNA repair, BRCA1 and BRCA2 are also involved in controlling the cell cycle and activation of apoptosis when all else has failed.

Shrink Exercise: Buster’s Unfolding

Buster Keaton GIF by Maudit

Buster Keaton was a master of visual comedy in the era of the silent movie. His use of props and perspective often brilliantly deflates presumptions on how things are supposed to be. In the opening scene of The High Sign (1921) the simple gesture of unfolding a newspaper turns into a beautiful shrink/growth exercise; in many ways more accurate than our A01 to A07 Exercise. Is the newspaper growing or is Keaton shrinking? And is it a coincidence that a small man appears on the pages?

Zebrafish Oannes

The zebrafish is one of The Incredible Shrinking Man’s most beloved spirit animals. Being a model organism for endocrinological and genetic research positions it between fact and fiction, the known and the unknown and the present and the future. Thus it invites us into realms of reality yet undiscovered. As mirrors of the human body they became subjects of desire and a reflection of deep physical wants. Yet at the same time they are part of the great unknown, the riddle of life, the majesty of the wild.

Lately the zebrafish has become somewhat of an iconic figure in our shamanistic dance routine, the Abun’dance. The dance represents the desire to break free from our dominant paradigm of continuous growth while illustrating and enacting the alternative perspective of shrinking. The fish on our feet perhaps symbolise the above mentioned desire as well as the notion of temperance, sometimes represented in western iconography by fish drawn or painted on feet. During some performances the dancer wears a lab coat painted (rather amateurishly) with fish scales. The ritual calls into memory the mythological figure of Oannes, the Babylonian fish/man hybrid that taught man the use of letters, sciences, agriculture, law, architecture and the arts.

Zebrafish Oannes disrupts comfortable understandings of how to attain the wisdom to reach abundance and prosperity for all forms of life: It is a call upon science to not just cater to the need for more but to also address and help forth  the desire for less.


Several years ago Dutch artist Joep van Lieshout suggested that rather than reduce human height to 50cm (as The Incredible Shrinking Man has investigated) people should shrink to the size of a parasite and live in the stomach of  a cow. It’s an interesting suggestion, not only because it opens up perspectives on collective use of resources, ecological connectivity and community but because it’s been done before, by size-shifting jellyfish also known as myxozoans.

Myxozoans are cnidarians, just like corals, sea anemones and regular sized jellyfish. In the process of shrinking the myxozoans lost their jellyfish characteristics to a degree that hadn’t been thought possible. “It would be like finding a one-celled creature and discovering that genetically, it’s a mammal that had lost its genes for lactation and keratinaceous hair”, explains team leader Dorothee Huchon of the Department of Zoology Tel Aviv University. During this process of extreme evolutionary transition they embraced a parasitic life, surrounding themselves with other organism’s organs so they need almost none of their own. Simple, effective, easy; just like Joep van Lieshout suggested.