Pitfalls of Science

[Charles]

Before proposing a theoretical solution to mutation, let's discuss the bacterial cell. It is a remarkable device or object. It has created the most dense digital storage medium (DNA) by far in existence and harnesses the second law to create mutations so that it can survive. Not only does this little creature harness the second law, in my humble opinion, it transcends the second law. Let me explain.

In the 1920's a physicist named Leo Szilard proved that digital information like DNA ought to obey the second law of thermodynamics. This should mean that as bacteria mutate their genomes should gradually degenerate. Thus, the end of bacteria. Well, tell that to a bacteria or a virus. Both thrive on mutation and need mutation to survive.

The other remarkable thing about bacteria is their development of an elegant digital code (the Universal DNA Code) and a digital molecule (DNA) from the very beginning of their existence. Now one would naturally expect the little buggers to develop biological digital networks to procreate (multiply) and create their proteins. You got an incredible digital storage medium, an incredible code, and the coding of this digital storage medium because DNA is a coded molecule. (DNA codes for proteins. Proteins are the building blocks of Life.) The little buggers also developed a means of expressing this digital information (the transfer RNA's and ribosomes) but incredibly, employ random chance not only to create new digital information but also to decode all their digital information in the form of transcription and translation. Thus creating substantial error in all their proteins. Bacteria "forgot" to develop the digital networks which could ensure 100% perfect replication, transcription, and translation. And thus the elimination of all error caused by the second law inside their little bodies. But did they really forget?

Because viral and bacterial genomes remain extremely robust and show no evidence of the deleterious effects caused by the second law on their genomes. In fact their genomes employ the second law to survive. Szilard says to them, "You must die". They say back, "We choose to live."

Humans should be so fortunate as I will explain below.

[cleeds]

Originally Posted by Charles

... I am a great believer in holistic medicine. To me it's all about diet and exercise. I take no meds, weigh 140 lbs, and walk about 50-60 miles per week. I have a home gym. When ever I get tired I think: cancer, diabetes, high blood pressure, stroke, and heart attack. This motivates me to keep going.

Medical science doesn't care about cures. It wants to treat. It would be devastating if disease was cured.

This is so very true although many people - including medical professionals - simply can't accept it.

For example, we've proven that heart disease is reversible. But of course there's much more profit in surgical and pharmaceutical interventions.

[Charles]

Originally Posted by cleeds

This is so very true although many people - including medical professionals - simply can't accept it.

For example, we've proven that heart disease is reversible. But of course there's much more profit in surgical and pharmaceutical interventions.

Cleeds, I appreciate your comments. I went to the dermatologist for my yearly skin check. He's a good friend of mine. We catch up on the news about our comrades in arms. A few months ago my personal physician and a good friend died of heart complications. He was much younger than me. Two days ago I learned of the death of a prominent physician and friend of mine from prostate cancer. He was probably 10 years younger than me. I was shocked.

Almost no one knows about my research. Why would they? I'm a superb clinician but not a basic science researcher. But biochemistry, DNA, the human genome and its organization have been hobbies of mine for 40 years. I've never published anything. I find biochemistry endlessly fascinating but as I have advanced in age, I do less and less reading.

Here's a few more comments/thoughts. I did not come to these thoughts overnight. They are the result of many years of study:

p.s. I left out mRNA. Messenger RNA is the copy of the gene that sets on the ribosome for translation. So you have the hard drive, i.e. the chromosome, the coded DNA, mRNA, tRNA, and ribosome, all digital molecules, but no digital networks. Digital networks really amount to an active process that supplies the enzyme with the correct base or amino acid, rather than relying on the passive process of diffusion. Relying on diffusion amounts to using the second law to supply the digital information to these elegant incredible molecular structures/machines. Just the enzymes are incredible molecular machines. The fact that they are capable of extremely accurately asking and answering the huge number of yes/no questions necessary for any cell to function, i.e. procreate and produce its proteins is remarkable. However, an active process would supply the enzyme in question with the correct piece of digital information 100% of the time. Suppose the enzyme made a mistake in a system with an active process. No problem. The active process would simply proceed to supply the enzyme again with the necessary/correct nucleotide or tRNA to correctly make the bond.

Suppose the active process was temporarily interrupted. No problem. The enzymes themselves can operate very accurately without it for an extended length of time with very low probability of significant error.

Below I will propose some elegant solutions and equations that theoretically eliminate the the built-in error created by the second law, i.e. diffusion. These solutions and equations amount to an active process as opposed to the passive process of diffusion. If these active processes were incorporated into human cells, disease as we know it would be eliminated. This is original work, my work.

Best

Charles

[Charles]

Before I post these equations and network(s) that would theoretically end mutation, I need to discuss protein Translation. Below is another large number:

"An average human protein is about 400 amino acids, which gives about 3⋅1020 proteins per hour." That's 3 times 10 to the 20th power 3e+20. I'll continue on later.

What this topic is amounting to is the digital nature of the human cell and the human body. Something you may not have given much thought to.

Some sources estimate the average human protein to be of length 500 amino acids. Also notice "length" because coming off the ribosome the protein is a linear sequence of amino acids. In human cells amino acids are added at a rate of about 5 amino acids per second and the error rate is estimated at 15% at best which is about 1 incorrect amino acid per every sixth protein. At worst it is about 1 in 1,000 codons or about one incorrect amino acid per protein. This means IMO that about 30-50% of the proteins in your cells contain an error. So if you lay around smoking and drinking heavily and are overweight, you might just be at the high end of this range. Not a good idea.

"For example, amino acid misincorporations during translation are estimated to occur once in every 1,000 to 10,000 codons translated1,2. At this error rate, 15% of all average-length protein molecules will contain at least one misincorporated amino acid."

Why and how is this error produced? Can it theoretically be eliminated? Understanding all this will help you to comprehend just how critical it is to maintain an absolutely healthy lifestyle. Stay tuned.

There is a phenomenon that occurs at every ribosome known as competition. Human cells have an average of 30 tRNA's from which all your proteins are built. Thus it may take numerous bonding attempts for a correct anticodon to bond with the codon setting on the aminoacyl site of the ribosome. I hope you can comprehend how important to eat so that your cells have an abundant supply of all amino acids. Each bonding attempt amounts to a yes/no question, i.e. to bond or not to bond. Since there are 30 tRNA's for 20 amino acids the chance may be about 1 in 20-30 that the correct one will show up providing everything is "perfect". Things are never perfect so say 1 in 30. So for just one protein this amounts to 15,000 yes/no questions the enzyme known as ef tu for bacteria (human cells have an equivalent), for one protein to be produced. This equals 4.5e+24 yes/no questions per hour the human body must ask and correctly answer for there to be 100% correct protein production, i.e. elimination of the 15-50% error.

The enzymes in the current human cell are not up to the task. And thus we see that at all levels: Replication, Transcription, and Translation very significant uncorrectable error is built in to or is inherent with every human cell. This is because the cell lacks an active process whereby the correct molecule, whether it be a nucleotide or an amino acid, is presented to the enzyme, whether it be the DNA polymerase, or the ef tu at the ribosome. In all cases human cells and in fact all cells rely on passive diffusion, i.e. the second law of thermodynamics and random chance to supply the needed molecule.

What is needed in the case of human cells is an active process. What is good for viruses and bacteria is no good for human cells.You are sick and dying because of the uncorrectable error built in to or inherent to every human cell. Stay tuned.

[Charles]

If I had to describe the difference between "analog" and "digital" it would be analog is characterized by unique "size" and unique "shape". Digital is not. Usually with digital the smaller the better. DNA is the densest information storage system possible. Your body has roughly 10 billion miles of DNA stored within it. When the protein exits the peptidyl site on the ribosome it is a linear sequence of amino acids created by digital processes known as Transcription and Translation. Then an amazing metamorphosis occurs: the protein bends and folds and acquires the physical properties of size and shape . It is these properties that determine the biochemical function of the protein. No super computer can string together a sequence of amino acids and predict the biochemical function of the artificial protein created by the bending and folding it would undergo. Creating a functional de novo artificial protein inside a computer is at this point in our development, impossible, much less in the laboratory.

Humans have about 20,000 genes. Estimates of how many proteins genes can produce vary widely:"The number of different proteins comprising the human proteome is a core proteomics issue. Researchers propose numbers between 10,000 [10] and several billion [6] different protein species." The prototype disease for abnormalities in protein translation, IMO, is Alzheimer's Disease. Accumulation of abnormal protein that interferes with neuronal function is its hallmark. What is the trigger that causes this accumulation? I don't know but it makes sense to, as you age, make sure that your brain has an abundant supply of protein (amino acids of all kinds) and nucleotides (DNA/RNA bases A, G, C, T &U). I like nuts for this reason although I don't over do it. Shelled pistachios and unsalted cashews are my favorites.

In my next post I will get into the nitty gritty of what it would take to eliminate human disease as we know it. Stay tuned. However I may receive a large batch of pics from my adult Science Project. Folks are relying me for an immediate response. If that happens it may be a week or two.

[Charles]

It's the middle of the night. I'll begin my discussion of the DNA Code soon since I have not received any pics. This stage of my Project is coming to an end and I suspect the computer graphics firm is going to present me with an overwhelming amount of work which I will immediately have to attend to. Covid 19 has slowed things down because we cannot meet, so the emails have to be precise.

One thing I can say about myself. I'm a superb clinician. I practiced emergency medicine for 34 years. Over that course of time I can count on the fingers of one hand the things I missed. I wrote a textbook on the subject I never published. I think my love of basic medical science and biochemistry really helped me. Also my love for Boolean algebra.

Most of my friends that I regularly converse with have advanced degrees. My dear physicist friend wants me to edit his book. I simply can't do it. I don't have time. I think you need to write your own books. Editing is tough. I'm no editor. However, he did calculate for me the the number of unique DNA Codes: 1.51010951579292000000E+84. There is out of this enormous number of potential codes, only one code we know of that works for Life. It is known as the Universal DNA Code. It universal to all of Life.

At this point I would ask you to step back and ask, "What to we have here? Where do we go from here? What conclusion(s) can be drawn?" I'll let you draw your own but let me say that the human body is enormously complex. There is always another enzyme or metabolic pathway. There is always another mutation, another disease. I ask again, "What conclusion(s) can be drawn from what we believe to be the knowledge in the reference biochemistry texts?"

Let me say, as a trained professional scientist, I think the wrong conclusions have been drawn and that medical science and science in general has been headed down a rabbit hole for a long long time.

I feel that medical science has failed me. Bob Dylan is my favorite poet. If I could meet one person in this life before I die, it would be him. Medical science and science in general is suffering from a disease so aptly described by this poem written by Dylan:

There's a whole lot of people suffering tonight from the disease of conceit
Whole lot of people struggling tonight from the disease of conceit
Comes right down the highway straight down the line
Rips into your senses through your body and your mind
Nothing about it that's sweet
The disease of conceit
There's a whole lot of hearts breaking tonight from the disease of conceit
Whole lot of hearts shaking tonight from the disease of conceit
Steps into your room eats into your soul
Over your senses you have no control
Ain't nothing too discreet about the disease of conceit
There's a whole lot of people dying tonight from the disease of conceit
Whole lot of people crying tonight from the disease of conceit
Comes right out of nowhere and you're down for the count
From the outside world the pressure will mount
Turn you into a piece of meat
The disease of conceit
Conceit is the disease that the doctors got no cure
They've done a lot of research on it but what it is they're still not sure
There's a whole lot of people in trouble tonight from the disease of conceit
Whole lot of people seeing trouble tonight from the disease of conceit
Give you delusions of grandeur and an evil eye
Give you the idea that you're too good to die
Then they bury you from head to your feet
From the disease of conceit

As a race we are dying because of this disease. Dylan knows it. It's all through his poetry.

Below I'll discuss the DNA Code as a preface to posting equations which if implemented within human cells would eliminate all mutation and errors in Transcription and Translation.

[Charles]

Just received some pics. May have to adjourn for a while. They are stunning.

A mutation may be defined as any change in your DNA.

In beginning the discussion of the DNA Code, I take exception with Voet and every other biochem text when it describes the Code as "degenerate". Voet states this because one amino acid is specified by more than one codon, often many codons. Voet states that "degenerate" is a term borrowed from mathematics (p.983).

Let me state that the DNA Code is not degenerate as defined by the use of the term in mathematics. The DNA Code is redundant, not degenerate.

This redundancy allows many mutations to remain silent: "Silent mutations are base substitutions that result in no change of the amino acid or amino acid functionality when the altered messenger RNA (mRNA) is translated."

In addition, the Code is arranged so that when a non silent mutation does occur the incorrect amino acid substitution is likely to have a similar polarity: non polar, acidic, or basic as the correct amino acid and thus maintain the integrity of the protein. According to Voet: "These observations suggest a nonrandom origin of the genetic code and indicate the code evolved so as to minimize the deleterious effects of mutations."(p.986)

I can't resist a critical thought or two at this point: I was taught that bacteria and viruses thrived off of mutations; needed mutations to survive. Also, since there are 1.5e+84 potential codes, seems randomness would be essential to determine which one would work the best.

Next, I need to discuss the concept of a code. What is a code? A code may be defined as a systematic standardized use of a given set of symbols used to represent information. All computer codes I know of are Boolean. Thus all computer codes must have only one output for the input and every input and output must be accounted for. No exceptions. All Boolean codes are powers of 2. Thus a 2 variable code has 4 inputs and 4 outputs. No exceptions. This fact creates the interesting condition called "don't cares" because not all inputs are usually required. Inputs that are never used can and must be assigned a value (either 0 or 1). These values (either 0 or 1) can be intelligently chosen to minimize and simplify the digital network. This property and necessity is craftily used by electrical engineers. An electrical engineer wants to design his network to have the fewest gates as reasonably possible.

The DNA Code qualifies as a Boolean code. Thus the DNA Code will have the variables A, G, C, T/U. It will have 3 variables equal to one codon. Each variable A, G, C, T/U will be worth 2-bits. So there are 64 inputs (codons) and 64 outputs (amino acids) with each input and output specified by the Code as it occurs in nature. Because there are 64 codons and 20 amino acids the Code may assign more than one codon to each amino acid. Gotta get to the treadmill.

[cleeds]

Charles, I'm trying to follow you as closely as I can on this. I'd be way over my head but for the help of my wife, who actually understands this stuff. That means you have attained an honorable achievement: The ability to get JoAnn to read an audio forum. (To be fair, she's pretty supportive of my audio and music pursuits, but does think frequenting an audio forum is a little nutso.)

Here's a question: Do you think damaged telomeres, which are at the end of the DNA (maybe also RNA?) strain, could allow the strain to unravel and result in DNA mutation???

[Charles]

I am continuing my discussion of the DNA Code. If I simply posted the networks it would mean much less to you, without some explanation. Also, don't forget the concept of "don't cares". This concept is fleshed out in the workings of the cell through the fact that in human cells only about 30 of the potential codons and anti-codons (tRNA's) are ever used. Thus fully 34 codons (34 inputs) are never used. They become in a sense the "don't cares" of the Code and the "don't cares" of the cell.

In biochemistry texts you will see this type of notation: ACU, ACC, ACA, ACG = Thr. What this means is these 4 codons each code for the amino acid Threonine.

Now let's write this expression in a more elegant Boolean expression:

Thr = ACU + ACC + ACA + ACG where each codon is a minterm and the "+" is the logical sum operator of Boolean algebra.

Thus the amino acid Threonine becomes equal to a minterm sum.

In fact, every amino acid and stop codon can be expressed this way, i.e. as a
minterm sum.

It is a fact of Boolean algebra that a minterm sum can be simplified to become a Boolean logic equation/function.

Thus each amino acid equals a Boolean logic equation or function.


Since there are 20 amino acids and a stop codon, the 21 outputs of the network for the Universal Code will equal these 21 Boolean logic functions, each logic function equaling one amino acid and one logic function for the stop codon. The inputs are the codons of the DNA Code. For any given cell only about 30 or so codons are ever used.

In order to create these logic functions and networks (I also have a network for the Code incorporating Selenium, known as the 21st amino acid, and also a network for the Mitochondrial Code), we must assign 2-bits to each nucleotide (A, G, C, U). U = the nucleotide Uracil. There are 4! or 24 ways to assign 2-bits to these 4 nucleotides. Each bit assignment results in a different assignment of minterms to each amino acid and stop codon.

For any Boolean network it is desirable to have the simplest most elegant network possible. Therefore we must create 24 networks composed of these logic functions and determine the number of gates necessary to create each network.

Each of these 24 networks represents about 20 minterm sums. Each minterm sum is composed of terms that are 6 variables each. Each minterm equals one codon. The minterm that is assigned to the codon changes according to the bit assignment but the codons assigned to each amino acid do not. They are fixed by the Code in nature. Without going into the details, this a truly daunting math problem but it is solvable. With considerable help I solved it.

Next, we then look at the 24 networks in terms of the number of gates and discover the one with the fewest number of gates. This network will have a bit assignment associated with it. This bit assignment should be the optimum bit assignment for the DNA Code.

Since there are 3 Codes: Universal, Universal with Selenium, and Mitochondrial, we must determine the optimum bit assignment for each Code by doing a similar analysis.

I hope that you can appreciate the complexity of this problem. A question arises: will the optimum bit assignment be identical for all three Codes? Will it be optimum for Transcription and Replication? in other words is the bit assignment as universal for Life as are the Codes?

I'm going to stop here. I just received a large batch of pics. Nevertheless, I will post the networks and optimum bit assignment on Sunday. Then I will continue on with some considerable explanation. I will also attempt to explain the "minterm". Basically, a minterm is a special one term (hence the phrase "min") Boolean logic function with amazing properties. I will elaborate by giving some examples but I want to get the networks and solution to the bit assignment posted first.

[Charles]

Originally Posted by cleeds

Charles, I'm trying to follow you as closely as I can on this. I'd be way over my head but for the help of my wife, who actually understands this stuff. That means you have attained an honorable achievement: The ability to get JoAnn to read an audio forum. (To be fair, she's pretty supportive of my audio and music pursuits, but does think frequenting an audio forum is a little nutso.)

Here's a question: Do you think damaged telomeres, which are at the end of the DNA (maybe also RNA?) strain, could allow the strain to unravel and result in DNA mutation???

Cleeds, thank you so much for the comment. Hold that thought until I finish. I'm glad your wife is interested.

Best

Charles