Robots continue to advance and develop every year, and these consistent improvements continue to amaze us with how much they physically resemble humans. Even though these robots lack spiritual qualities and function way below the human brain, we still admire these developments, for they lead to even more discoveries and help us understand the miraculous human body even more.

Notwithstanding our medical knowledge that continues to build upon nearly 3,000 years of shared human experience and research, new discoveries about the human body, the magnificent work of God Almighty, continue to increase our admiration.

The discovery of the “Interstitium” and the “Subcapsular Proliferative Foci” in 2018 allow us to develop an even greater appreciation for the complexity of our bodies. They are called the “macro organ” and “micro organ” according to the amount of space that they occupy in our bodies, along with the nicknames “buffer organ” and “control center organ” according to their function. These newly discovered biological structures did not attract much attention earlier because, in accordance with our current understanding, organs are more easily visible structures such as the hands, arms, eyes, nose, kidneys, and lungs that have a certain shape and a set of clearly-defined functions. It is interesting that although these complex structures are so widespread in our bodies, they were not known until recently; they are now considered as organs [1].

The Macro Organ: Interstitium

According to an article published in Scientific Reports on March 27, 2018, the “interstitium” was discovered rather serendipitously by David Corr-Loce and Petros Benias of Mount Sinai Beth Medical Center along with Neil Theise, a pathologist from New York University. The discovery came when these physicians were analyzing a cancer patient’s bile duct. Although they had been conducting the same routine over the years, it was the first time they had the sight of slots between examined tissues. They realized that the interstitium was unnoticed earlier due to the disappearance of interstitial fluid after they had examined the tissue with their usual histological methods. Subsequently, the researchers found that this structure was found not only in the bile duct but also in many other organs.

Specifically located under our skin, these micro-compartments were also found in almost all organ membranes except the intestines, lungs, veins, and muscles in order to form a network around the organs with malleable but sturdy proteins. The interstitium, the entirety of the intercellular spaces filled with liquid, has been defined as the largest organ in the body. Actually, examining cells and tissues has been the subject of histology and cytology science for the last 150 years, and the fluid that fills the tissues and forms a basis for supporting these cells was not new to the medical world. However, its definition as a new organ was a first.

The researchers froze the biopsy tissues obtained from the bile ducts of 12 patients in order to preserve and examine the anatomy of the discovered structure. One of the reasons that this organ exists is because it protects the surrounding organs by acting as a shock-absorber and has an effect similar to that of a car’s bumper. Damage to tissues and internal organs remains minimal when one falls, hits something or is impacted Using a micro-endoscopic camera, the volume of this whole organ was revealed to be about ten liters in an adult human [2].

It was later discovered that the interstitium is also present in the structure of lymph nodes, the most important part of the body’s immune system, and that cancer cells enter the lymphatic system through the interstitium. In this case, the interstitium play a significant role as a passageway, or conduction interface, for spreading cancer cells across the body. In an analogy, this organ is akin to the water in which fish swim, the air that surrounds us, and the soil that borders the roots of trees. In this liquid that rotates the cells and spans on the base where they are positioned, any exchange of substances of body biochemistry is regulated within the required amount and size to provide a good setting to the cells, and the hard mechanical effects that may impact the cells are alleviated and absorbed by this liquid pad.

Each discovery of the interstitium’s features, including its significant contributions in the fight against cancer, reveals more and more about how this great organ aids in intercellular communication.

The Micro Organ: Subcapsular Proliferative Foci

One of the most important features of the immune system is that it has its own “memory.” The cells of the immune system can remember the infections a person has contracted before, and can fight infections before they spread. How quickly the immune system reacts based on memory may vary, for instance depending on the type of infection, but is usually quite rapid. Considering how many bacteria multiply in a matter of seconds, a quick response must be launched to prevent infections from spreading across the body.

Professor Tri Phan of the Garvan Medical Research Institute led the team of researchers that discovered the subcapsular proliferative foci (SPF), a “micro-organ” that appeared in the lymph nodes during an infection. Lymph nodes and lymphoid organs such as tonsils, thymus, and spleen are surrounded by a protective capsule made of connective tissue. This capsule was considered to serve the purpose of a mechanical support only to enclose and protect the lymph nodes. However, recent research has shown that in some areas under this capsule, cells that had been alerted to previous encounters with harmful invasive organisms are gathered. These main subcapsular cells are memory B cells that carry information on how to counter the invasive organisms. Memory B cells also proliferate into plasma cells, which are highly important for producing antibodies. Therefore, when an infection reoccurs in our body the subcapsular proliferative foci act quickly to form the first defensive front to prevent the possible spread of infection.

The purpose of vaccines is to activate the attenuated form of a harmful organism to be stored in the body’s memory as an immune response. If the body comes back into contact with similar bacteria in the future, the immune system will remember how to fight it. The discovery of the sub-capsule foci also revealed that these centers are the home for the memory B cells. If they can unveil the development and training processes of the memory B cells in these slots, scientists can produce vaccines that enhance the memory of the immune system even more quickly and efficiently.

The reason why these structures have not been noticed earlier is due to their emaciation, brief emergence, and disappearance. The sub-capsule proliferation centers presented in the article “Memory B Cells Are Reactivated in Subcapsular Proliferative Foci of Lymph Nodes” published in Nature Communications on August 22, 2018 are defined by some authoritative scientists as the “micro-organ.” According to the findings about this new organ, if our infection-fighting immune system would have activated longer than it currently does, we would easily die. Every minute is very crucial in this struggle. These excellent centers that produce memory cells under the lymph node [3] capsules fight bacteria which can replicate in multitudes every 20–30 minutes during an infection.

Although the world of science has been working with the microscope for about 400 years, these centers that have been embedded in our body since its creation could only be noticed today when the microscope design has reached its technological peak.

There are trillions of bacteria living in the intestinal cavity, skin, and orifices of our body. Some of these are already protective and beneficial, yet others are pathogenic. But they do not make us sick because of B cell production centers. When our immune system is weakened for any reason (such as stress, insomnia, or malnutrition) these bacteria can cause illnesses and meet little resistance. These sub-capsular micro-organisms surrounding the lymph nodes were placed in the most strategic places across the human body to fight infections in the fastest way, while the lymph nodes were placed at locations that are most vulnerable to microbial attack.

Consequently, these discoveries increase our admiration for the palace and magnificent realm called our body. It is likely in the light of this information that the anatomy and histology books may be rewritten and the definitions of organs and tissues may be redefined.

References

• Claire Maldarelli, “Scientists found a new organ, but it might not be what you’re expecting,” Popular Science, 3 April 2018.
• iflscience.com/health-and-medicine/newly-discovered-microorgan-helps-explain-how-vaccine.
• nature.com/articles/s41598-018-23062-6

With all of its faculties, a human being can be thought of as an index of the whole universe. Therefore, we witness correlations between the processes taking place in the human body and in the universe. Accordingly, the world we live in has a correspondence to human biology. For example, the cyclical processes in the environment (water cycle, carbon cycle, etc.) ensure the continuous recycling of the same matter, hence the cleanliness of the habitat for all. Similarly, the human body includes mechanisms to cleanse itself from harmful and unnecessary materials.

Prior to the development of such an understanding, the prevailing attitude encouraged consuming natural resources and using the environment as a “trash can.” Even today, we live in a world that promotes excessive consumption of daily goods leading to accumulation of incredible amounts of trash. For example, in developed Western societies, an average family discards more than one ton of trash every year, which is mostly paper, packaging material, and kitchen waste.

Nevertheless, as we realize the importance of the recycling systems in nature and the multi-faceted harms of trash accumulation on the environment, recycling of conventional and technological waste is encouraged by collecting plastics, glass, paper, and tins. On a larger scale, recycling centers have been developed to minimize the damage to the environment and to meet the need for raw materials.

The recycling process consists of three main steps as depicted by the famous three-arrows symbol representing 1) the collection of materials, 2) the remanufacture of new materials from the collected ones, and 3) reselling or reusing as new products. Thus, recycling centers not only contribute to the economy, but also serve as clearance sites to maintain the harmony of the environment.

Cellular recycling through “fasting”

Similar to recycling centers at the macro level, there are recycling centers in the cellular level too. These centers have the duty to help with the digestion of cellular trash (i.e. damaged cellular organelles, misfolded proteins, toxic load) so that energy can be generated and raw material obtained for the construction of new cellular units. This recycling phenomenon was simply named as autophagy (i.e. self-eating) by cell biologists. What is interesting, though, is that autophagy is primarily activated or enhanced via fasting or food deprivation.

How autophagy works

Autophagy is a process that occurs when astarving cell starts to form double membrane containers through an orchestration of several proteins. These containers are called autophagic vesicles or autophagosomes ¹. Their main role is to target and collect cellular trash. Then, they start to fuse with lysosomes, the digestion centers of the cells, to degrade the trash into building blocks—amino acids. The amino acids can then be used both for the construction of new proteins needed by the cell and in the production of ATP, which is a source of energy for the cell.

The whole process corresponds to micro-scale representation of a real world recycling concept: collection, re-manufacture and resell/reuse. Through autophagy, a cell recycles its own material and obtains energy ².

Fasting: An emerging trend

With the discovery of mechanisms initiating autophagy and its involvement in various diseases such as cancer, neurodegenerative disorders, auto-immune diseases etc., autophagy has gained a unique significance that is progressively increasing ³. After the year 2000, the number of publications on autophagy-related research began to increase exponentially. Moreover, due to the increased conviction about the link between fasting and autophagy, fasting started to become a real trend in modern civilizations. Let’s examine a few of the important recent findings that reveal the relationship between autophagy and fasting.

In a study involving mice, the response to fasting was assessed in liver cells (hepatocytes) by tracking the presence of a protein (GFP-LC3) that indicates autophagy. It was seen that the lack of food, which is the source of energy, led to the disintegration of mitochondria, which are the power plants of the cells. Subsequently, the components that made up those mitochondria were re-utilized for the building of other necessary proteins⁴. These results indicate that unnecessary mitochondria were eliminated for the sake of recycling organic materials during fasting.

Neurodegenerative diseases, such as Alzheimer’s or Parkinson, etc, are linked to the accumulation of trash in the brain cells, which is indicative of a lack of autophagy. Drugs developed for these diseases do not possess effective treatments since they are unable to penetrate into the brain cells (a concept known as the blood-brain barrier). During another study involving mice, in one track, animals were exposed to fasting, and in the other, their brain cells, (more precisely cortical neurons and Purkinje cells) were isolated and exposed to food deprivation. In both tracks, researchers observed that fasting enhanced autophagy, suggesting that fasting could be a simple, cheap, and safe therapeutic cure for prevention of neurodegenerative diseases ⁵.

In another study, this time involving a subset of kidney cells (proximal tubule cells), a lack of autophagy resulted in the accumulation of dysfunctional mitochondria and other cellular debris. As a result, the cells grew in size abnormally (hypertrophy), decreasing the functionality of the kidney. This suggested that autophagy was part of the continuous maintenance of proximal tubule cells and that inducing autophagy in the kidney may provide a novel therapeutic approach to minimize acute kidney injury ⁶.

As a final example, one more study revealing the association between autophagy and the immune response should be mentioned. It was found that the number of autophagic vesicles (chambers) in the macrophages, a subset of immune cells that are the first to perceive threats to our body, increased as a response to invading bacteria. These vesicles wrapped, sequestered, and digested the bacteria eaten by macrophages ⁷. Thus, fasting has the potential to improve the fighting ability of macrophages against invading pathogens by enhancing autophagic machinery.

Taken together, the autophagy process seems to be a recycling mechanism with minor variations depending on the cell type and activation triggers. Once initiated, it leads to a) reduced accumulation of cellular trash (toxic protein aggregates); b) an improved immune response for removing bacteria (intracellular pathogens); and c) the protection of the interior of the cell (cytosol). As one of the main stimulators of autophagy, fasting or food deprivation seems to be a way for improving health.

Next time you fast, keep in mind that while you are starving, your cells are feasting for your health. Just as the natural world is structured to continually cleanse and renew the earth, fasting seems to trigger similar processes inside the human body. While individuals may choose to fast for spiritual cleansing, their physical bodies experience a cleansing as well.

Abdullah Acar is freelance writer in the US with a special interest in biology.

References

1. Mizushima, N., et al., Autophagy fights disease through cellular self-digestion. Nature, 2008. 451(7182): p. 1069-75.
2. Mizushima, N. and M. Komatsu, Autophagy: renovation of cells and tissues. Cell, 2011. 147(4): p. 728-41.
3. Yang, Z. and D.J. Klionsky, Eaten alive: a history of macroautophagy. Nat Cell Biol, 2010. 12(9): p. 814-22.
4. Kim, I. and J.J. Lemasters, Mitochondrial degradation by autophagy (mitophagy) in GFP-LC3 transgenic hepatocytes during nutrient deprivation. Am J Physiol Cell Physiol, 2011. 300(2): p. C308-17.
5. Alirezaei, M., et al., Short-term fasting induces profound neuronal autophagy. Autophagy, 2010. 6(6): p. 702-10.
6. Kimura, T., et al., Autophagy protects the proximal tubule from degeneration and acute ischemic injury. J Am Soc Nephrol, 2011. 22(5): p. 902-13.
7. Fujita, N. and T. Yoshimori, Ubiquitination-mediated autophagy against invading bacteria. Curr Opin Cell Biol, 2011. 23(4): p. 492-7.