Micro Deaths Create Eternal Life

@midjourneybot: /imagine: immortality

Micro Deaths Create Eternal Life

This essay is part 2 of “The BioLogical Robot”. If you haven’t read part 1, you should start there. In part 1, we learned how our chromosomes work like “tape drives” to protect our DNA source code. Chromosomes constantly spool and unspool the DNA tape only where it needs to be read. We learned how genes in human DNA are interoperable with the genes in fruit flies and that some sections of our “DNA tape” haven’t mutated one single letter in 1,000 million years.

It may be surprising to learn that some portions of our DNA tape are sacrosanct, or Read-Only Memory (ROM). And just as surprising, DNA can modify portions of itself during its own lifetime. Most of the cells in your body are running slightly different versions of your original source code. They are competing to better fit you into your current environment.

Computer scientists have a similar process for updating source code while it’s running that we call Runtime Patching. There’s so many things that can go wrong when runtime patching, that software designers generally avoid doing it at all costs. Sometimes when software updates are off by just a single letter, it can crash the entire machine. Software is that brittle and as we’ll see…so is our DNA.

DNA Evolution

There are several ways that DNA can modify itself during its own lifetime.

The first method is called Horizontal Gene Transfer (HGT). Our DNA can actually acquire and test new genes (software packages) from foreign invaders by stealing segments of their DNA. Theoretically, our chromosomes can not only acquire genes from our parents, they can also try out genes they encounter during our lifetime. Horizontal Gene Transfer is the most prolific source of mutation in bacteria. When a bigger bacteria eats a smaller bacteria, it tries out its software. HGT is not known to be as common in animals, but there are scientific examples of bacteria-to-bacteria HGT, bacteria-to-animal HGT, and animal-to-animal HGT. Here’s a whitepaper called, “Horizontal gene transfer between bacteria and animals” for more:

HGT in animals and bacteria

Remember, there’s 0.00% mutation in 1,000 million years for the genes that make the histone “spools” that hold this mutated DNA “tape”. That means the new DNA source code has to splice together perfectly—there are exactly 147 DNA pairs for every 8 histone spools.

The interoperability of our genes is amazing, but every design has vulnerabilities. Geneticists have determined that roughly 1% of the DNA in humans are ancient and recent viruses. These are called Human Endogenous Retroviruses. Viruses are just strings of RNA, floating around the universe, looking for protein factories to hijack. Retroviruses come with a special Reverse Transcriptase protein that can insert their RNA into another organism's DNA, just like a computer worm.

Our code is 1% DNA worms.

But these may not all be “DNA infections”. Here’s a quote from the National Institute of Health describing Human Endogenous Retroviruses, “Over 20 HERV families have been identified during the past two decades. Although many are defective through the accumulation of mutations, deletions, and termination signals within coding sequences, a limited number of HERVs have the potential to produce viral products and, indeed, to produce viral-like particles.”

As a computer scientist looking at DNA as machine code, these code snippets with “termination signals within coding sequences” sounds a lot like nerds describing antivirus software. For example, if you look through the machine code of Norton Antivirus, we would see segments of code that are nearly identical to the StuxNet computer virus. But Norton isn’t infected with StuxNet, it just retains parts and pieces of StuxNet code so that it can kill it on sight in the future.

The mRNA platform from Moderna works the exact same way. When the biology nerds who sequenced the COVID-19 virus sent the DNA sequence of the protein spike to the biology nerds at Moderna…they emailed the G, A, T, and C sequence in Microsoft Word. The Moderna mRNA platform added that COVID-19 protein spike to an innocuous bacteria, which taught our immune systems the “signature” of the COVID-19 virus. That way, when the real COVID-19 virus shows up, our immune system murderbots the virus faster than it can replicate.

I was vaccinated with Moderna, so somewhere inside me is DNA source code that originally came from nerds in Microsoft Word. 🤯

So our DNA mutates from Horizontal Gene Transfer, viral attack, nerds with computers, but also physical friction in the real world. Occasionally extra nucleotides get added or deleted from a DNA sequence during replication. Geneticists call this “wobble” or “strand slippage”. Cells make millions of copies of their own data during their lifetime, so to prevent mistakes of even one letter they use a process known as Mismatch Repair (MMR). After the replication process is complete, the resulting RNA output is compared to its DNA template. Here’s a quote from Cell Research magazine that discusses the importance of this process, “MMR corrects DNA mismatches generated during DNA replication, thereby preventing mutations from becoming permanent in dividing cells. Because MMR reduces the number of replication-associated errors, defects in MMR increase the spontaneous mutation rate. Inactivation of MMR in human cells is associated with hereditary and sporadic human cancers, and the MMR system is required for cell cycle arrest and/or programmed cell death in response to certain types of DNA damage. Thus, MMR plays a role in the DNA damage response pathway that eliminates severely damaged cells and prevents both mutagenesis in the short term and tumorigenesis in the long term.”

DNA Mismatch Repair

Here’s another good whitepaper about how errors in DNA become mutations.

DNA Replication and Mutation

The MMR System is critical to understanding our software design. Our cells were designed to copy the same code perfectly to the letter INDEFINITELY. If human DNA was designed, then we were intended for immortality. At least our code is.

Evolution and natural selection don’t just happen between generations. Cells within our body mutate constantly (evolve) and drastically cull their weakest performers (natural selection). Evolution and natural selection are happening within our lifetime. This allows us to better fit our environments, indefinitely. I’m not saying Darwin is wrong even though I kinda am. At best Darwin is right the same way that Sir Isaac Newton is right in Physics. Newton is right until we change the scale. The formulas don’t really work when we zoom out to space. We need Einstein. Newtonian physics don’t work when we zoom in either, we need formulas from Heisenberg and Planck.

So let’s zoom in and look at the evolution and natural selection of individual cells.

You, me and everyone we know started life as an ovum. This was a single living cell that contained the original diploid source code donated from each of our parents. The ovum is the only time humans are in “mint condition”. As our ovum interacts with the universe it starts getting smarter. The software may try out new genes it encounters, it may get hacked by RNA worms, or it may change its own epigenetic code to improve cell regulation within its environment. When this cell divides, it performs what computer programmers call a Project Fork.

Here’s the wiki: “In software engineering, a project fork happens when developers take a copy of source code from one software package and start independent development on it, creating a distinct and separate piece of software. The term often implies not merely a development branch, but also a split in the developer community; as such, it is a form of schism. Grounds for forking are varying user preferences and stagnated or discontinued development of the original software.”

You are not just one DNA sequence anymore.

All 37 trillion cells in your body forked from code that forked from code that forked from your original ovum. The best reason to constantly fork our software is to A/B test its performance. Computer programmers do this constantly. For example, the Facebook app on iPhone doesn’t just have the source code to make a little menu bar along the bottom of your screen. The Facebook app has code to make 50 different versions of that menu bar and they “live test” which versions are the best performers…ON YOU. If your Facebook app menu has been the same for a while, that probably means their algorithm is satisfied with your “engagement metrics”.

Geneticists are seeing more and more evidence that our non-protein-coding DNA is changing and adapting faster than we thought. Geneticists have been calling this part of our source code “Junk DNA” since the 1960’s. Here’s a quote from Medical News Magazine. Dr. Ananya Mandal MD explains it well, “In a Nature review published in the 1980, Leslie Orgel and Francis Crick stated that junk DNA ‘had little specificity and conveys little or no selective advantage to the organism.’ However, over the years, researchers have found evidence to suggest that junk DNA may provide some form of functional activity. Some lines of evidence suggest that fragments of what were originally non-functional DNA have undergone the process of exaptation throughout evolution. Exaptation refers to the acquisition of a function through means other than natural selection. In 2012, a research program called the ENCODE project concluded that around three quarters of the noncoding DNA in the human genome did undergo transcription and that almost 50% of the genome was available to the proteins involved in genetic regulation such as transcription factors.”

Scientists have detected transposing jumping genes in embryos that are only 5 days old.

Jumping Genes

It might seem weird that all the DNA in your body doesn’t match at the same time. It doesn’t. There’s a chance that some of your DNA didn’t even match the rest of your body at birth. Here’s a fascinating story in Time magazine about a dad who is actually his own kid’s uncle. Using the miracle of modern genetics, the dad learned he suffered from vanishing twin syndrome. So 10% of the sperm he produces today actually carries the DNA of his twin brother who was cannibalized in utero. It’s almost as if the attacking DNA never quite finished its job because the dead twin not only lives on inside him, it reproduced a new human. This dad only shares roughly 25% of his genes with his own son.

Dad is Uncle

We can visually confirm the variations in our own DNA software just by looking at our skin. A freckle on our skin is not just a single cell that “forgot” how to make the right skin pigment. At some point in the past, the sun damaged the genetic code that determines the correct pigment our skin cell. The MMR System in that cell won’t notice the unintentional mutation when it comes time to replicate, so it has no problem passing the mutation on to its daughter cells. These daughter cells won’t get culled as long as they are doing a good enough job with their other functions so eventually that one cell “blooms” into a whole family of cells that share this change to the source code.

DNA Natural Selection

With all the innumerable opportunities our cells have to mutate, pruning the underperforming DNA from our body (natural selection) is just as integral to our design as mutagenesis (evolution).

Our bodies start this process long before our birth. For example, in the book “Genome: The Autobiography of a Species in 23 Chapters” (paid link), Matt Ridley describes how aggressively the female body culls the variations in its source code. He writes, “In the ovary of a five-month-old human fetus, for example, there are nearly seven million germ cells. By birth, there are only two million, and of those two million, just 400 or so will be ovulated during the coming lifetime. Most of the rest will be culled by apoptosis, which is ruthlessly eugenic, issuing strict orders to cells that are not perfect to commit suicide (the body is a totalitarian place).”

@philosophers: If humans have an intelligent designer, then our designer decided that women can be trusted with one precious egg per month, while men can only be trusted with 100M new sperm per day. This is one reason I strongly support gender quotas in the US Congress. If 50% of our law makers were women, then our budgets for war and education would “mutate” significantly. 

This drastic pruning takes place in our brains too. Ridley writes, “The brain is born with far too many connections between cells; many are lost as it develops. For example, at first each side of the visual cortex is connected to one half of the input from both eyes. Only by fairly drastic pruning does this change so that one slice of the brain receives input from the right eye and another slice receives input from the left eye. Experience causes the unnecessary connections to wither away and thereby turns the brain from a general to a specific device. Like a sculptor chipping away at a block of marble to find the human form within, so the environment strips away the surplus neurons to sharpen the skills of the brain. In a blind, or permanently blindfolded young mammal, this sorting out never happens.”

When the MMR System works perfectly, it culls all the underperforming code from our “software repository” which allows us to become perpetually fitter to our environment. When cells die perfectly according to plan, the organism lives forever. This is why most of the longevity research is focused on the MMR system.

At the forefront of this research is David Sinclair and his “Information Theory of Aging”. He presents it well in his book, “Lifespan: Why We Age and Why We Don't Have To”.

His theory, like many others in this book, is built upon “Information Theory” by Claude Shannon. You can also watch Sinclair presents his research in a 15-minute TED Talk:

Here is a one hour interview with Dr. Lee Hood, MD, PhD. followed by some highlights from the conversation.

  1. Sinclair’s “information theory of aging:” Built on mathematician Claude Shannon’s work on information heory, Sinclair asserts that the replicating efficiency of DNA codes degenerates over time as “noise” enters the system. This noise leads to “breaks” in DNA sequences. It is these breaks in DNA sequences, not the DNA itself, that cause aging.

  2. Degeneration occurs in “reader” cells: Genes and their epigenetic expression propel cell development and differentiation. The body contains two basic types of cells. The first type contains each individual’s genetic data or DNA. The second type reads and directs DNA application. Throughout the translation process, the archival DNA copies remain pristine, but the “reader” cells degrade over time from the signaling noise described above. Sinclair equates these degenerating DNA “reader” cells to “scratched CDs” that don’t play music as well as they once did. Fix the “scratches” and aging slows.

  3. Aging is a disease: Sinclair’s research suggests that these “scratched” reader cells are treatable. From a medical perspective, he believes it is easier to slow or even reverse cell degeneration (i.e., aging) than to treat many forms of cancer. If true, this represents a monumental shift in medical reasoning. Aging causes 85% of all human suffering, including most major diseases. The ability to treat aging as a disease and slow its detrimental impacts has the potential to extend healthy human life well into the 100s.

  4. Aging is a simple three-level mechanism: The first level encompasses environmental inputs, including eating and exercise, that influence the aging process. Adaptive behaviors, stress to the immune system, such as intermittent fasting and experiencing cold, can extend an individual’s lifespan. The second level consists of specific longevity genes, such as sirtuin proteins, that repair cells under stress. These repairs modulate the pace and extent of the aging process. The third level is the fundamental relationship between DNA and its application, captured by Sinclair’s information theory of aging. In Sinclair’s opinion, it is now possible to proactively influence this relatively simple structure.

  5. Practical advice: Throughout the discussion, and especially during the audience Q&A segment, Sinclair discussed his own strategies for managing his immune system and extending his lifespan. They include eating one meal a day, exercising big muscle groups and taking supplements to enhance his longevity genes. These supplements include metformin, rapamycin and resveratrol. It’s never too late to start combating aging. Upon retirement, Sinclair’s 81-year-old father changed lifestyle behaviors and now is in better shape than Sinclair himself.

What's fascinating about David Sinclair’s research is that using intentional errors to DNA replication, his team can artificially age a living mouse. These young mice get fat, slow down, and their hair turns gray just like the rest of us. More importantly, Sinclair can reverse age a living mouse by “polishing out the scratches” in its DNA record using a process called methylation. All the information to stay alive forever is already present in our DNA, our DNA just fails to read itself accurately.

With lowering costs to CRISPR based gene repair, improved DNA methylation and MMR management, future generations may finally eat from the Tree of Life. Unless our grandchildren are accidentally or intentionally murdered, they may have to choose to die.  Sinclair argues that we’ll cure cancer as a by-product of curing aging itself.

When humans eliminate aging, it will eliminate one of the strongest certainties in our reality. America co-founder Benjamin Franklin once wrote, “Our new Constitution is now established, everything seems to promise it will be durable; but, in this world, nothing is certain except death and taxes”. Future Americans will need to update his quote to, “Our old Constitution is still established, everything but social media seems to promise it will be durable; but, in this world, nothing is certain except uncertainty and taxes”. Taxes aren’t going anywhere, taxes are more certain than death. Even if there were only two humans left on Earth, the weaker one would get taxed.

Today, we already use CRISPR based gene repair to cure single letter mutations like Sickle Cell Anemia in Victoria Gray. What’s important about Gray’s repair is that scientists gave her a bone marrow transplant with herself. The single letter change to her DNA is now being propagated throughout her body. Within 18 months doctors stopped seeing sickle cells in her blood. When she dies, if she dies, she will die with “root” source code different from what her parents gave her.

Victoria Gray will just become “patient zero” for editing your own DNA sequence during your lifetime. In ten years, changing my eye color to green or growing thick curly hair might just be a CRISPR shot in the arm. All I have to do is wait seven more years for my software upgrades to replace all the molecules in my body.

The percentage of people that get addicted to cosmetic surgery will become just as addicted to cosmetic DNA. I started this book with a quote from Arthur C Clarke which states, “The only thing we can be sure of about the future is that it will be absolutely fantastic, so if what I say now seems to you to be very reasonable then I’ll fail completely. Only if what I tell you appears absolutely unbelievable will we have any chance of visualizing the future as it really will happen.” Well, a century from now the Earth may actually look more like the X-Men movies. The source code that makes wings in birds will work in other animals once we decipher all the internal dependencies. Future humans may incorporate gills for breathing underwater and have silverback gorilla strength. How many future NBA hopefuls will “upgrade” their software to become Shaquille O’Neal’s size? They might even be able to license Shaq’s DNA to do it. Corporations like Monsanto are already copyrighting and licensing DNA for fruits and vegetables that “outperform” their wild counterparts.

We’ll close this section on chromosomes with a short 6-minute video from Veritasium to see our “tape drives” in action. It’s called “Your body’s molecular machines”.

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➡️: Nanobots and Microbots

⬅️: The BioLogical Robot  

⬆️: Table of Contents

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