BIOLOGICAL MESH NETWORKS

 Biological Mesh Networks

 

We are a collection of cells. We never think about it or probably don’t know that each one of those cells is individual unicellular organism with its own innate intelligence. These cells come together to build a higher life form to improve chances of survival. All evolution is about survival. Individually each cell is much more vulnerable but collectively it can build attributes that would protect it better. But ironically to be part of such collective self it has to sacrifice its own life for the betterment of the whole whereas if it was not part of such collective self it would use its innate intelligence and desire to survive to make itself immortal. We call such cells that break free from the collective self cancer cells. For the higher form to remain operationally and collectively stable the cells are bound together with ‘mesh’ networks. The cell towers that give signal to our millions of cell phones have an interesting architecture where each tower is not just connected to its neighbour but all cell towers are connected to each other like a mesh. This is done to create automatic, intelligent load sharing between them. That way if there is conference or a festival at a certain area it won’t overwhelm the cell towers in its vicinity. Instead the extra load is shared with whichever towers that have much lower utilization regardless of how far or near they are. That way every cell tower helps the other.

 

Mesh Network Topology

 

In our biological mesh networks cell completely changes its persona and priorities to that of the collective organism. This may not be its natural state and so is held tightly on a leash by multiple mesh networks. One of the most recently discovered mesh network is bioelectrical by a brilliant scientist called Professor Michael Levin at Tufts University. I would encourage everyone to see his fascinating videos available on YouTube.

Michael Levin PhD

Another one is a physical mesh network connected by filaments protruding from each cell connecting to each other in a 3D network. The one that my own research works on is Extracellular Messaging Network. Each cell secretes tiny bubbles with various molecules which find another cell and inject that cargo of molecules in the receiving cell. This exchange too is constantly happening amongst and between our more than 30 trillion cells.

Michael Levin has proposed a major change in how we treat diseases. He suggests that the way we currently do so with our obsession with DNA and single molecules and CRISPR gene editing is similar to how programmers changed programs on computers in the 1960s:

By repatching the hardware every time the program needed to be changed. But now it can easily be done systemwide without touching the hardware using only the operating software and recoding it. What we have managed with these manual repatching of hardware is mostly management of symptoms with hardly any full cures of chronic diseases. No wonder 90% of the drugs fail to be approved. It would be much more powerful and effective to reprogram cells through the mesh networks that hold them tightly together. He demonstrates this by taming the most difficult disease ever: cancer. In a young, healthy body the cells are polarized in the bioelectrical network. They are always depolarized in disease and aging. Cancer cells too are depolarized. Michael Levin’s lab hyperpolarized the cancer cells and voila! Like magic they become normal cells. When cells break free from the collective organism all other cells become their host cells and they multiply and proliferate rapidly to ensure survival. They use their innate intelligence to outwit their hosts collective defense networks and tools. But as soon as they are pulled back into the collective self then they lose that independent selfish desire to thrive and survive and become a slave of the collective will. By changing them from depolarized state to hyperpolarized they come back to what we would term as normal behaviour but in reality there is no right or wrong behavior just different personas depending on whether they are part of a collective society or individual single cell organism like an amoeba. Can you imagine us as collection of amoebas? J

What this highlights is the future of medicine: Using any of the mesh networks to resolve a disease state. One can also consider aging as a disease state that we can also resolve in a similar manner.

So there are three levels of intelligence: innate intelligence of each cell, collective intelligence of the mesh networks and neurological intelligence of the higher organism. Although we call multicellular organisms a higher form the distributed innate adaptive intelligence that cells have seems far more superior to the higher form. Without having a central neural network to have the ability to analyze and take complex decisions the cell is able to use its internal, individual bioelectrical, biochemical and genetic/epigenetic networks to become a distributed intelligence. What incredible, incredible engineering in such a tiny, crowded space! Levin showed us through experiments that the bioelectrical network hosts sequential information about spatial organization of a higher form which builds us from a tiny single egg to a complex adult: the program of development.  But where is the sequential information stored on the program of aging? The collective intelligence has a group plan for building a multicellular life form and also a group plan for its operations. Cells that have partial disruption in their mesh network connections manifest into a disease and when they are completely disconnected from the group mesh networks and group identity they become selfish and cancerous.

Professor Michael Levin gives an amazing example of the collective intelligence: He loves to research with Planaria worm because it has evolved some astounding abilities. If it is cut into pieces, each piece is able to grow into a full, exactly same proportioned worm. What is in that cut off piece of that worm that has the distributed memory of its own full architecture and also instructions of how to regenerate exactly the parts needed at exactly the correct location to conform to the original worms architecture. Levin has shown evidence that this information is stored in its bioelectrical mesh network. In another example of collective intelligence: When planaria is inserted in barium its head blows off because it can not survive in barium. In a few days it regrows a head that can survive in barium. How does it activate only those genes that would allow its head to adapt to barium? So not only does it’s collective intelligence design a brand new head and position it correctly but it also changes its tissue material and properties so that it can survive in barium. Think about it: such a tiny worm without its head making decisions about which tissue material would be able to withstand barium! and then which genes to activate and close to produce that tissue as part of the regenerative scaffold! Beyond belief! This same collective intelligence also builds us in correct proportions into a full blown adult starting from a single fertilized egg. Imagine the power we would have if we can code or manipulate this collective intelligence stored in a mesh network? Our current tools like CRISPR seem so advanced and revolutionary but are primitive and unidimensional compared to this tiny worm's collective intelligence. We are so used to intelligence associated with dense neural networks in our brains that it’s very difficult to imagine such brilliant collaborative intelligence without any ‘brain’ or neurons. Where would such analytical computing machine be residing?

This tiny worm's mesh networks are more evolved and more advanced than us humans.

Another mesh network is what I call Extracellular Messaging Network or EMN. YUVAN uses this mesh network to make system wide changes. 

Extracellular vesicles derived from young plasma rejuvenates aging cells through multi-modal improvements by hacking the EMN. It’s like inserting new code to correct operating software errors in a computer. 

Besides bioelectrical network and chemical exchange through physical filament network, cells also communicate with each other via lipid enclosed molecules like proteins and RNAs. Almost all cells constantly secrete these messages in extracellular vesicles (EVs) or in protein conjugates. These EVs naturally do a molecular ‘handshake’ with other cells and inject their cargo of proteins, RNAs and more not only into the recipient cell but also into its nucleus. This cargo then executes their function: for example, a miRNA may bind to a protein and neutralize it or a non coding RNA may make epigenetic change which could affect a gene’s expression. This exchange again is like a mesh, so not just between neighboring cells but across distances with cells in far off locations transported there in circulating plasma. This intercellular messaging is constantly going on from even before we are born till death. Each cell is influencing the epigenome, transcriptome, proteome and gene expression of other cells through this messaging network. Some exchange is targeted to a particular cell through surface proteins called tetraspanins regardless of how far the recipient cells are located.

 

Next generation of medicine will hack into or leverage these intercellular mesh networks to gain system wide results. Levin is developing actuators/switches to manipulate the bioelectrical network to gain Planar worm type of regenerative superpowers. YUVAN has been harvesting EVs and some more plasma constituents from the plasma of the young mammals around puberty. As at that age the messaging cargo is supporting a near homeostatic efficiency in cells. As I have mentioned in my previous posts aging and disease result from ‘epigenetic drift’. A quick recap: all cells have the same DNA then why some cells become a heart cell and another becomes a liver cell – both so different. This is due to epigenetic configuration. Each cell type has its own unique epigenetic template that shuts down around 80% of the genes and keeps open the balance. Which gene is shut and which is left open decides the cells form and function. During embryogenesis these epigenetic marks are wiped clean and a fresh template is installed for each cell type during differentiation. But in almost all multicellular organisms this epigenome begins to lose it’s configuration in some places leading to what some scientists call ‘epigenetic drift’. This can result in partial or full loss of cellular function. As more and more cells progressively get misorganized parts of their epigenome, their tissue or organ can lapse into a disease. Aging is another manifestation of this epigenetic drift. Around puberty such epigenetic drift has not started and body is at its peak to support reproduction. So YUVAN harvests EVs and other plasma constituents around puberty and injects them into older recipients. This basically hacks into the EMN. As per natural process these EVs inject their cargo into older recipients cells. Now the proteins and RNAs circulating in the young influence the epigenome, transcriptome, proteome and gene expression of the older cell. This reverses the epigenetic drift and resets the epigenetic configuration closer to it’s pristine template found around puberty. And voila! the cell begins to function like a young cell.

Modern medicine has been priceless for so many infections and diseases that used to kill us previously but it hardly gives us any full cures. Mostly managing symptoms. Focusing on a single gene or a few genes or a single protein or antibody doesn’t produce a full transformation or regeneration of the diseased tissue or organ. That’s why 90% of the drugs fail to get regulatory approval. Whereas a drug that can influence any of these mesh networks can reprogram the entire network or any part of it to a more efficient form. A tiny worm has adapted its survival mechanism, won during evolution, to regenerate and repair any epigenetic disorganization instantly as we would heal a small wound. This results in a stable epigenome the importance and benefits of which is the subject of my previous blog post titled Stability = Lifespan. A stable epigenome keeps the cells healthy and efficient leading to youthful immortality of the Planar worm. We can see a similar ability to keep its epigenome stable in Ginkgo Biloba tree which is much bigger than the worm. It too has been called immortal. We are a collection of cells. Of all the parts of a cell why is epigenome the most important? Because it is what gives each cell its identity and function. In aging and disease we see a gradual loss of both leading to various painful complications and eventually to death. Reprogramming our biological software to cure epigenetic disorganization is the future of our medicine. Can we learn from the worm and the tree to modulate our endogenous mesh network softwares to stabilize epigenome in each of our cells and then maintain that stability forever?