The Role of Regenerative Medicine in Modern Warfare

It is a sad truth that aggression and war have always been a part of the human history. There has never been a time when the world globally has been in its entirety at peace. Unfortunately, a closer look at the events in the international arena doesn’t provide us with even a glimpse of hope for a diversion from this pattern in the foreseeable future. With the progress and development in science and technology under way, more and more sophisticated weapons are being produced, having vastly devastating impact in the warfare conduct. (ICRC, 2013) (Chinedu Cletus Ude, 2018)International law falls short when it comes to enforcement of the prohibition of many of the deadliest ones.

Although use of chemical and biological weapons have been prohibited by the international humanitarian law, reality shows disrespect for the international conventions. (ICRC, 2013) Yemen or Syria can be mentioned from the recent cases. I believe that if result of the progress in science and technology is many times a culprit in human suffering, it can and should also be used for remedying it. Thus in my research, I have decided to attempt to examine the possible positive impact of regenerative medicine in the modern warfare. Medical, scientific and descriptive approaches were adopted as a basis for analysis. Modern Warfare: Technology has always been the source of improved tools of warfare. In the contemporary age, systematic research in science and medicine has preconditioned and made feasible development of new technology and innovations for use by both military and civilians. This development has had effects both on the society and the nature of warfare. (Modern-Warfare, 2018) (Bohr, 2018)The person himself who would now be known as the father of chemical warfare and was first to exploit chemical weapons was in reality his own guinea pig to test his invention first hand.

On April the 2nd, 1915, Fritz Haber, the head of Berlin's Kaiser Wilhelm Institute of Physical Chemistry, moved into the yellow-green cloud of chlorine gas on the ground that was back then used for troop exercises. The test was successful. Haber, a war enthusiast started coughing rapidly and grew pale, due to which he had to be carried on a stretcher. (Modern-Warfare, 2018) (Bohr, 2018)Around three weeks later, German forces used this chemical agent for the first time on a mass scale during the combat on the Western front near the Flemish city of Ypres in Belgium, where they deployed an approximate amount of 150 tons of the substance. This marked a first in world history, a successful usage of chemical weapons on a mass scale against humans. What would ensue in latter combat was a more widespread usage of chemical weapons.

Although the allies condemned this incident, they too began using chemical agents on the field. (Modern-Warfare, 2018) (Bohr, 2018) (Hughes, Chemical weapons: The day the first poison gas attack changed the face of warfare forever, 2016)Innovations such as this are mostly conducted at times of conflict. Inventions such as the telephone, fighter plane and many more were explored throughout times of conflict. This, unsurprisingly is also when CBRN (Chemical Biological Radiological Nuclear) weapons were looked at.

The nuclear bomb came out towards the end of the second world war, and that is where we can see a clear path for modern warfare. WW1 and WW2 have been bridges for modern warfare to emerge. A type of conflict where quantity is compromised over quality. Aspects of war that are more practical and high in both damage and raw destructive power are preferred to older more primitive ways of fighting. (Modern-Warfare, 2018) (Bohr, 2018)However, nations are spending more on the destructive capabilities of technology rather than on the human condition. What we can see as a common factor in most weapons nowadays, they are physical and exploit living organisms incapability to heal fast enough. Damage is done faster or way more severely than the body can repair it. Therefore current funding is being shifted slowly but steadily towards medical advancements. (Modern-Warfare, 2018) (Bohr, 2018)Regenerative Medicine: Regenerative medicine is a branch of translational research in tissue engineering and molecular biology which deals with the "process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function".

This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs. Treatments today can be summed up into three roots; Tissue Engineering and Biomaterials, Cellular Therapies, Medical Devices and Artificial Organs. What the main issue with all of these is that they need a surgical environment for treatment. This means that they can’t be deployed on a wide spread basis to the field. That’s why researchers are currently looking at other conservable and durable opportunities that are easy to apply. Although nothing that resembles these guidelines is currently feasible to use, or simply does not exist, they are experimenting. Stem cells have been a site for many to turn to. Stem cells are cells that have the unique ability to develop into any specialised cell of the body. They can undergo self-renewal, which means that they can undergo multilineage differentiation and form terminally differentiated cells. Whether that is a nerve or red blood cell, they can do it all. This is important because our body is made up of cells, where most cells are specialised to do a specific task, such as red blood cells that carry oxygen in the blood, but can not divide. Stem cells create new cells for the body as it grows, or replace lost or damaged cells. They have two properties that enables them to do this; they can divide over and over again to produce new cells, they can change into any cell whilst doing this. (Nesti, 2011)There are two main stem cell groups in a human body; Embryonic stem cells and adult stem cells.

Embryonic stem cells:

• Embryonic stem cells are the cell supply for growing embryos.
• These stem cells are pluripotent, which means that they can develop into any cells in the body.
• These are derived from developing embryos.

Adult stem cells :

• These cells are the supply of new cells for organisms as they grow to replace lost or damaged cells.
• They are called multipotent, which means they can develop into only a set of cells, not all.
• These are derived from the body at any stages and at any age.

Adult stem cells are existent in every tissue of the body, from brain to internal organs and to fat tissue. (Tiryaki, Tiryaki, Calabrese, & Findikli, 2016) These cells can be harvested from any part of the body but usually the number of the harvested cells are very limited, so there is a need to send them to a laboratory and culture them in order to get enough cells to be used as a treatment modality. On the other hand, fat tissue has much more stem cells in comparison to other tissues. These are called fat derived, or adipose derived stem cells (ADSC). Due to the high number of ADSC in fat, and the easiness of harvesting the fat tissue from the body without causing any damage to the vital functions, fat tissue became the primary source of stem cells in modern medicine. In practice, fat tissue is surgically harvested from the body using liposuction cannulas in a very simple way. Later it goes through a separation process in which enzymes are introduced to separate the stem cells from the fat tissue, and finally centrifuged for total separation. 500cc of lipoaspirate enables us to get 200 million regenerative cells. All this process of fat harvesting and stem cell isolation takes around 1. 5-2 hours.

Due to these characteristics, adipose derived stem cells may be an ideal candidate for global militaries to consider as treatments. However, as everything, stem cells have shortfalls that make them severely limited for military usage. Even though the only stem cell linage from the above stated, capable to prove highly in military usage are adipose derived stem cells, still, this all requires surgical treatment, both on the extraction and insertion. Stem cells are also fragile, where they are not durable enough to withstand hardly any other conditions than laboratory conditions. They are open to many sorts of exposure and have a limited life.

Stem cell treatment is also limited, whereby they can be used for radiological damages to cure cancer or exposure to radiation, but hardly anything else other than chemical or biological threats. This means no traditional combat wound healing.

Stem cell treatments are also too expensive for wide usage. Future of Regenerative Medicine in the Military: This does not mean that regenerative medicine will stop right here. There are still many possibilities, and a need for new treatments. As far as many people are concerned, feasible treatments are in need. Exosomes may be the solution to this. Cells communicate with each other using cytokinesis. These are proteins excreted by a cell that tell another cell what to do. Stem cells work on the same basis, creating a repair sequence throughout cells. Exosomes are little packets that leave off the outer wall of cells. (BMCBIOL, 2016) They can carry proteins and mRNA. However, what is important on exosomes is that they can carry mRNA. This is big, because mRNA makes protein. It is like a set of instructions for the proteins to be synthesised. These proteins can be anything from building blocks to chemical signals. What connects exosomes to stem cells you ask? Exosomes can be found in the culture media when a stem cell is being grown or cultured. (Hildreth, 2017) Due to exosomes containing mRNA and cytokinesis, harvesting these and injecting them into a patient to stimulate repair has been proposed. However, this is not all that simple. (Centeno, 2018)

An exosome is just like a missile fired towards a target cell by a stem cell. It has a payload, which can either contain protein to tell the cell what to do or mRNA to force the receiving cell to produce proteins that the stem cell needs. This can be used for repair. (BMCBIOL, 2016)What complicates these exosomes is what makes stem cells admirable. Stem cells detect their environment and act accordingly. Repairing cells is a complicated orchestration of cells receiving the right stimulus at the right time. The problem about harvesting exosomes from a stem cell culture is that they are specific to growing more cells in the culture. Given that stem cell culture is not a repair environment, more a growing environment, it has little to do with a repair situation, useful for more complex injuries. Therefore, these exosomes are like ‘dumb missiles’, missiles with the wrong payload. (Hildreth, 2017)When stem cells are present in an environment in need of repair, they release exosomes carrying proteins and mRNA specific to repair. These ‘smart bombs’ are also directed to specific cells that are involved in the construction of cells in a local region, and release exosomes carrying a different inventory at different times. All of this combined, are signals what the region of damage needs for repair. (Centeno, 2018)This is a wonderful source of regenerative cells. It is also durable, can be mass produced and cheaper than other options on the current market. However, this is not on the market. We do not yet fully understand exosomes, the firing sequence and targeting protocols of stem cells. What I mean by this, we do not know when, why and at what the stem cells do send exosomes, or with what sort of payload they are sent. Culturing stem cells is also not permitted in the US, because they are not fully understood and are unapproved as a drug by the FDA (Federal Drug administration).

This is an issue as the most common way to obtain exosomes is by stem cell culturing, and the US is one of the few places with sufficient resources for this to be carried out on a mass scale. (Metrics, 2008) Obtaining exosomes from amniotic fluids is also not an option as this is also an unapproved drug. This all means that funding is necessary for research for such therapies to emerge. (Centeno, 2018)There are however some possible uses of exosomes in the near future on the field of combat. If sufficient research is done, and its results are positive, exosomes may be mass produced to be made into pre-prepared packets of treatment, capable of deployment on the field. This would make them practical and cost effective, as immediate appliance of the product would be possible due to the simplicity of it’s usage, resulting for reliable and sterile wound treatments. Conclusion: Emerging modern warfare fields have resulted in few parties holding huge destructive power, capable of devastating results. This risk of heavy losses has necessitated for improved treatments, both in quality, effectiveness and ease of use. Current treatments that are almost in usage include stem cells. (Tiryaki, Tiryaki, Calabrese, & Findikli, 2016) They can be used to treat exposure to radioactivity. (Chinedu Cletus Ude, 2018)

Therefore they can be seen as in the scope of military usage. However due to midterm shortfalls of stem cells, more powerful treatments will be needed some time after stem cells are introduced. Exosomes with many comparative advantages such as easy deployment, durability, variety of treatment and easy usage will with a high probability take the lead in regenerative medicine, mainly in combat injuries. Peace may not be acquired as quickly as these therapies emerge, therefore a more widespread method of remedy, with much better quality than in use is in need. Peace may not be guaranteed. However, we may try harder to ease the suffering.