Dear Maria,

Chanelling chaos, pre-determined or tamed chaos - I am not sure that can explain it qualitatively. Here Mezut as I see is profi. I assumed it from some readings long ago, from information theory, from Ilja Prigogine. If you have not read his " Order from chaos" - I recommend very much. You can find it in Russian. Once I did a work on transdifferentiation, where this pre-determined chaos was seen very clearly, it is published but as you are not a biologist, I shall try to explain simply. It was shown that state of cells 1 is changed after trauma into state 2, which is another type of cells, in fact, It occurred through a series of intermediate states, many of them were erroneous (I had a method to estimate this by their production in electron microscope) - chaotic mixture of the product (often found in cancer). It is called amianthoid. And erroneous intermediate cells died but likely also they conditioned (channeled) the nearest environment. A lot of sorting. So, it went through two weeks until the necessary phenotype (state 2) was achieved and all stabilised. But the process was pre-determined by the gradient of the natural inducer causing state 2. Literary, each time as a cell divided in two, the daughter cell which was on the side of this inducer underwent these changes towards state 2, while another daughter usually stayed like their mother. So, it happened - step by step. Likely I sent this article to Mezut. Till now I am impressed by this process. Besides experimental articles, I described it and some other examples in the small review article, please, see attached.

With best wishes, Katrina

Dear Yekaterina,

Thank you for your question and for the articles you've sent me. Am I right that you'd like to have a mathematical model describing (supporting) the life-cycle idea? It seems to be interesting but couldn't be done at once. First, I'll try to understand exactly what it is about - reading your articles and maybe some other ones. I've sent you a request for another article of yours but never mind, I've already found it.

As to your question, I didn't mention those two theories because I never heard about them :) Being a mathematician, I'm relatively new in this field.

Dear Maria,

You are courageous - my compliments, a scientist should be such!

These are the non-linear, low probable processes.

Therefore I have the logo - two smiley in one - for my friends.

It would be interesting to prove the inevitability of cancer as a consequence of complexity - to say simpler - we tribute with cancer for complexity and the possibility to me witty extravagant mathematicians, for example.

Dear Jekaterina,

Thank you for the compliment and for the logo!

To prove the inevitability of some low probable event is not a problem - mathematically it surely will happen if we have enough trials. To me, the problem is to develop a model which fits the epidemiological data (SMT failed at that).

But why are you so sure that cancer is inevitable? Not everyone gets it. I've examined some SEER incidence rate data for two cancers, transformed rate (which is not a comprehensive characteristic of cancer start time) to probability density function (PDF) and found out that it decreases after some age, which means that those who are alive at that age have less cancer chances than the youngest ones.

I've developed a one-hit model which takes into account immunity decreasing with age. Maybe "immunity" is a wrong word and we have to speak about the tumour suppressor function (as in your article) instead? If you are interested, my model is very shortly described here: Conference Paper Mathematical Models of Carcinogenesis developed by Medical S...

(the last section).

My e-mail is there if you decide to continue our discussion in private.

P.S. I'm not courageous, I'm curious :)

Dear Maria,

Multiple working hypotheses of cancer you can find here (24 hypotheses):

https://www.researchgate.net/publication/328637334_The_detached_pericyte_hypothesis_A_novel_explanation_for_many_puzzling_aspects_of_tumorigenesis

Dear Andrzej,

24 - it's great! The only thing we have to do now is to find out which 23 of them are wrong. The remaining hypotheses should be the one we are looking for :)

However if not a single one of them... but let's not talk about the sad things.

To be serious, I read several papers of that author but didn't meet this one, thank you for sharing.

Dear Maria,

Carcinogenesisis not inevitable but probalistically associated with age. SMT has failed through the Cancer Genome Sequencing Project and this is accepted by those who wishes to see the reality (see two articles attached, one - by guru of cancer research). Who does not wish to see it - continue their business.

Inevitable is escape from treatments of most cancers which have mutated (or inactivated) the main tumour suppressor TP53. It is called cancer resistance to damage (killing). I am working on that 20 years and in several hundreds experiments, the tumour cells ALWAYS escape (sometimes begin re-growth only 4 weeks after killing treatment). My conviction is that you cannot kill a cancer cell (and in our last article, it is explained why - it is an acquisition of 4 billion years of life evolution) but you can... tame (normalise) it, at least to the level stopping metastases. People began to work on that. It is symbolocally that R Weinber is writting on the full circle - in fact only the first proliferative circle was considered. But cancer cells also have another one, reciprocal reproductive circle. It is more complex. The two circles support immortality of a cancer cell. Kind regards.

Dear Jekaterina,

Association with age is what any model of carcinogenesis should be checked with. If the model doesn't explain the existing data then smth is wrong with the model.

SMT failed with sequencing, you are right. But it could fail more than half a century ago if only a good mathematician examined it at that time. Unfortunately, mathematicians rarely read medical journals.

The very idea of a multistage nature of carcinegenesis came from mathematics made by biologists and there are several mistakes in it. Mathematics is a dangerous field where falsity implies anything. That means that until the theory (model) contains mistakes, it conclusions mean nothing.

But medical researchers took SMT for granted and spent decades searching for magical sequences of 5-6-7 mutations and publishing tons of articles about that. Moreover, not only medics were involved. I know personally some mathematicians who believed that doctors had really found that mutations. Those mathematicians made their careers studying the mathematical consequences of multistage theory and its particular cases.

Just as Poincare said "Everyone is sure that errors are normally distributed since the experimentalists believe that it is a mathematical theorem, and the mathematicians that it is an experimentally determined fact".

Again and again medical researchers develop mathematical models by themselves and start to believe in them. The Bad Luck theory by Tomasetti and Vogelstein is a good example. It is full of gross mathematical mistakes but many cancer specialists still take it seriously.

You doctors often tell us: "Don't cure yourself" and you are right. We can say you the same: "Don't do math on your own".

Thanks for the links (of course I've already read the impressive article by R.Weinberg).

Best regards.

Dear Maria,

You say: Association with age is what any model of carcinogenesis should be checked with. If the model doesn't explain the existing data then smth is wrong with the model.

But this is not a model but reality. Everybody knows that cancer mostly appears in elder people. There is also big-data epidemiological statistics on that. I used some epidemiological curves in my lectures on carcinogenesis many years ago, now there should be more and better.

In turn and paradoxically, the association of cancer with age is part of the embryological or atavistic theory of cancer because senescence of stem cells bears a reversal potential (on a single-cell level it can make a life-cycle-like circle returning from the end to the beginning of life). This is a model. To comprehend it, you need deep knowledge of developmental and evolutionary biology, which not each biologist and medical doctors have. And we need the people who can help as a bridge to physics and math. F.ex. an outstanding system biologist and specialist in

statistical mechanics Prof. Alessandro Giuliani. Please, get a look at his site. Alessandro is a very agreable person, you can find a mutual tongue with him.

With kind regards,

Katrina.

Dear Katrina,

You say: Everybody knows that cancer mostly appears in elder people. There is also big-data epidemiological statistics on that.

You are right. But the increasing can go in different ways. It is well-known that SMT doesn't fit the existing epidemiological data. Many authors had written about that, for example the last paper which I've met is Working Paper The stem cell division theory of cancer

The character of the epidemiological curve can say smth about the character of underlying processes to a mathematician. I'm trying to get that information out.

Would you be so kind to give me a link to Prof. Alessandro Giuliani site? I'm interested in your recommendation but I'm a bit confused as there are several researchers with that name.

Best regards,

Maria

SMT = somatic nDNA mutations + somatic mtDNA mutations, and it should work or still not?

best regards,

Andrzej

Er... SMT=Somatic Mutation Theory. Not equal to mutations + mutations.

1. The mathematical foundation of SMT is good for nothing (my paper with mathematical analysis of it is submitted and I have no idea whether I may share it now).

2. SMT doesn't have any other foundation.

3. About the results of genome sequencing Jekaterina Erenpreisa will tell better than I will. To my knowledge, they didn't find mutations associated with cancer in the tumors but have founded them in the healthy tissues.

To me, points 1-2 are enough to abandon SMT while point 3 is the last nail in its coffin.

Best regards,

Maria

Have been somatic mtDNA mutations also checked (or only somatic nDNA)?

SMT = somatic nDNA mutations + somatic mtDNA mutations, and it should work (but of course sometimes not, there are exceptions).

best regards,

Andrzej

Again, theory (T) is not equal to the sum of mutations, is it?

What do you mean should work? Theory? No. Mutations? I think they do.

Where both sorts of mutations checked via sequencing? No idea, let's wait for Jekaterina's answer.

Best regards,

Maria

Dear Maria,

Somatic mtDNA mutations should be also taken into account when SMT is considered. If so, then SMT is not so bad... (but of course sometimes are exceptions and for these cases SMT seems not ok)

best regards,

Andrzej

Can you give any link?

Dear Maria,

There is a lot about it on the Internet, for example:

"Somatic mutations of mitochondrial DNA have been detected in various pathologies such as cancer, neurodegenerative diseases, cardiac disorders and aging in general"

https://www.researchgate.net/publication/7558823_Somatic_mutations_in_mitochondria_The_chicken_or_the_egg

https://www.researchgate.net/publication/46148239_Somatic_mutations_of_mitochondrial_DNA_in_aging_and_cancer_progression

https://www.researchgate.net/publication/23458916_Mitochondrial_DNA_Mutations_in_Cancer_A_Review

https://www.researchgate.net/publication/51138550_The_Importance_of_Mitochondrial_DNA_in_Aging_and_Cancer

https://www.researchgate.net/publication/7160624_Significance_of_somatic_mutations_and_content_alteration_of_mitochondrial_DNA_in_esophageal_cancer

https://www.researchgate.net/publication/40728629_Mitochondrial_DNA_in_tumors

https://www.researchgate.net/publication/11051524_Accumulation_of_mitochondrial_DNA_mutations_in_ageing_cancer_and_mitochondrial_disease_Is_there_a_common_mechanism

https://www.researchgate.net/publication/321605250_Mitochondrial_DNA_Mutations_in_Aging_Disease_and_Cancer

best regards,

Andrzej

Thank you.

Dear Maria,

SMT is ok (of course sometimes are exceptions), but not so easy to understand.

regards,

Andrzej

Dear Andrzej, I'm so sorry that I forgot to write to you after you kindly sent me all those links.

I don't know whether SMT is OK, but I know that first, its mathematical foundation is wrong and second, it doesn't have any other foundation. Thus I don't see any logical reason to believe in it. But belief is not always based on logic, is it?

My editor forbids me to reveal any details until the publication of my research about that (I'm working on the revision just now and not sure it is the last one). I'll share here the link when (if!) it is published.

And detecting mutations (whether mitochondrial or not) within tumors don't prove that the mutations are the cause of cancer - maybe they are its companions or consequences...

See the opinion of Ilya B. Tsyrlov, the former Senior Scientist at NCI, NIH, and now a President & Chief Scientific Officer at XENOTOX, here (the first answer):

https://www.researchgate.net/post/Are_there_any_experiments_confirming_that_driver_mutations_are_the_cause_of_cancer_not_merely_its_companions_or_consequences

.

Dear Maria,

Thank you and regarding your question "how justified is the statement that smoking (and some other carcinogens) increases the probability of cancer?" - have you found the answer to this question? If not, I will send you an article about it.

regards,

Andrzej

Dear Andrzej,

I did find some answers but didn't find them completely satisfying so I'm interested in other ones.

Regards,

Maria

Dear Maria,

Maybe in this article you will find a satisfying answer:

https://www.researchgate.net/publication/324951917_Cigarette_smoke_and_chewing_tobacco_alter_expression_of_different_sets_of_miRNAs_in_oral_keratinocytes

and this article is about technology to fight this cancer cause:

https://www.researchgate.net/publication/265969951_Mir-34_A_New_Weapon_Against_Cancer

regards,

Andrzej

Thank you, Andrzej!

Dear Andrzej,

Bhat, at al describe "alterations in miRNA expression in oral cells" in response to using tobacco. Then they claim that those alterations MAY BE involved in initiation of ORCC. "May be" means "and may not be" doesn't it?

I believe that using tobacco lead to some alterations in the body but I didn't see, in that article, any explanation how those particular alterations result in cancer, except that some proteins were found to be overexpressed in multiple cancers. Was it a cause or a consequence of cancer remains unknown.

A lot of alterations in our bodies occur over time, you yourself had shared with me the paper where 24 theories of cancer occurence were listed. Bhat et al don't even try to prove that tobacco using is a cause of cancer, they postulate this.

It's funny that at that they refer to Mona Saraiya, et al "US Assessment of HPV Types in Cancers: Implications for Current and 9-Valent HPV Vaccines" which is not about tobacco using at all.

Regards,

Maria

Dear Maria,

Smoking causes inhibition of ETC and as a result fATP destabilization/dysregulation and as a result mitochondria overenergization and as a result cancer transformation ("Case 1 - bioenergetic problems" in https://www.researchgate.net/publication/326302952_Bioenergetics_of_life_disease_and_death_phenomena)

regards,

Andrzej

Dear Andrzej,

Thank you. The conception of the UCB is completely new to me, so I need some time for understanding what it is about.

Regards,

Mariia

Dear Andrzej,

I'll not even pretend that I've understood at least half of your article :) Nevertheless may I ask you several questions?

1. Am I right that you consider the altered energy metabolism (AEM hereafter) as a cause of cancer and smoking as one of the causes of AEM?

2. Are there any quantitative data linking smoking with AEM and AEM with cancer? E.g. 3 cigarettes per day result in 55 measurement units (what are they?) of AEM, and 10 measurement units of AEM mean the probability 0.2 of getting cancer in a year? If no, do you have any ideas how to get such data?

3. Can your theory explain the following two things:

- the Churchill syndrome, I mean living a long life without getting lung cancer though smoking like a chimney?

- the decreasing of cancer risk at older ages?

4. You write that "Driver mutations in cancers of the same type are also typically different" referring to Kaufmann, 1971. If so, how can we hope to know what mutations are driver? I looked through the Kaufmann's article but didn't find even the word "driver" there.

I apologize if the answers are inside your article, maybe I just didn't find them.

Regards,

Maria

Dear Maria,

Thank you for reading my article and points.

1. In accordance with the unified cell bioenergetics (UCB) cancer is caused by destabilization/dysregulation of positive feedback for ATP (fATP destabilization/dysregulation) what can lead to overenergization of mitochondria.

2. Smoking can cause overenergization of mitochondria filling them with high energy molecules (especially NADH). So, data should be connected with higher NADH levels during smoking.

3. a) "the Churchill syndrome, I mean living a long life without getting lung cancer though smoking like a chimney?" - yes, it is easy to explain using UCB (He happily did not get cancer).

b) "the decreasing of cancer risk at older ages?" - the rate of metabolism can decrease so much (at older ages) that the risk of mitochondria overenergization also decreases.

4. Please see also "Tumors of the same type typically show no congruently overlapping but quite differing sets of driver mutations" [ref. A].

[ref. A] in my article: Huang S, Ernberg I, Kauffman S (2009) Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective. Semin Cell Dev Biol 20(7):869–876

This article is here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754594/#R36

regards,

Andrzej

Dear Andrzej,

Thank you for your answer.

3a). How? I mean what is that explanation? Obviously some people are more susceptible to cancer while the other are less susceptible. What is that individual feature, according to UCB, that defines that susceptibility?

3b). This is exactly what I'm looking for! Did you ever meet any graphs about metabolism rate vs age? If so, can you give me a link (or any hint)?

4. Thank you, I'l read it.

Regards,

Maria

Dear Maria,

In accordance with UCB, mitochondria overenergization increases probabilitity of cancer transformation and also increases probability of apoptosis.

In my article:

"Apoptosis—higher NADH levels cause a higher rate of ROS generation, which can lead to severe oxidative damage to biolipid membranes, proteins and DNA (see Remark 3). Mitochondria normally initiate apoptosis when damage to the respiratory apparatus becomes critical (..)

Cancer—cells that do not undergo apoptosis can be transformed into cancerous ones (see Remarks 1, 3)"

Maybe some specific predispositions of his cells to apoptosis protected him from cancer.

regards,

Andrzej

Thank you Andrzej.

Dear Maria,

Welcome

"Cancer arises through the accumulation of somatic mutations over time"

https://www.researchgate.net/publication/331737577_In_silico_learning_of_tumor_evolution_through_mutational_time_series

regards,

Andrzej

Thank you, Andrzej.

Dear Andrzej,

"Cancer arises through the accumulation of somatic mutations over time" - the authors postulate it. This is a standard beginning of many papers.

Nothing new. A lot of people believe in SMT, I know it.

Moreover, there are a lot of people believing in much more strange things :)

Belief is not proof. Never.

Dear Maria,

I know - I believe, if I feel that something is true. This preprint is from 2019 (i.e. it is new), and this is why I've presented it you.

regards,

Andrzej

And I'm grateful for that as it keeps me informed that things don't change. There are still many researchers for whom their belief is more important that knowledge.

Neither your nor mine, nor anybody's else feelings are about science.

Physicians sometimes feel (believe) that a particular treatment works. Evidence based medicine then proves than their feelings have deceived them, see for example

https://www.amazon.com/Ending-Medical-Reversal-Improving-Outcomes/dp/1421417723

Regards,

Maria

Dear Maria,

Believing, we gather knowledge, striving for uncover the truth. But what is truth? A good question asked a long time ago to God.

regards,

Andrzej

Dear Maria,

This article can be interesting for you:

https://www.researchgate.net/publication/331608382_Estimating_the_number_of_genetic_mutations_hits_required_for_carcinogenesis_based_on_the_distribution_of_somatic_mutations

"Several factors, other than genetic mutations, may also affect carcinogenesis, such as epigenetic modifications [20], tumor environment [21], and adaptive evolution [22]. However, carcinogenesis is primarily a result of genetic mutations [23, 24]. Somatic mutations in particular are a critical driver of carcinogenesis, as exemplified by the occurrence of cancer in Caenorhabditis elegans and Drosophila melanogaster"

regards,

Andrzej

"Believing, we gather knowledge..." Not "we" :) A lot of researchers use another paths to knowledge. Not bothering any gods.

Thank you for sharing the paper.

Maria

Dear Maria,

In my opinion, the reason of cancer can be considered as disturbances in the observed by us fantastic, beautiful and incredibly complex project (the project of DNA code of all living organisms with the possibility of evolution).

These disturbances can be caused by:

- Case 1 — bioenergetic problems,

- Case 2 — genetic problems,

- Case 3 — cell interaction disruption;

as it is in my article.

regards,

Andrzej

Dear Andrzej,

Smth happens because of either bioenergetic problems, or genetic problems, or cell interaction disruption... Taken together with embriological cancer theory and atavistic theory (Jekaterina Erenpreisa), with chaos theory of carcinogenesis (Mezut Tez), and with many other theories it means only that...

indeed, smth happens which triggers cancer.

I agree completely, smth happens. We only have to found out what it is, and which of those alternative theories (if any) has anything to do with reality.

By the way, maybe this article

https://www.nature.com/articles/d41586-018-07737-8

can be interesting to you as to the fan of multistage model.

Regards,

Maria

Dear Maria,

Cancer transformation causes cancer, so cancer is triggered by cancer transformation.

Bioenergetic problems, genetic problems, cell interaction disruption can cause cancer transformation.

regards,

Andrzej

Smth that happens is an initial mutation which causes cancer as an adaptive response to this crucial change through reprogramming (in general, the cause is a disadaptation - may be not genetic mutation, anything - lack of oxygen, etc). The adaptive response is in fact banal - it is borrowed from evolution of very distant pro-and eukaryotes and includes the pre-programmed events (metabolic, polyploidisation f.ex.) which, in order to be realised with the survival chance close to zero should use the chaotic systems (including transposons - Tez Mezut). So, the chaos is channelled. It all is rather known. I really do not understand what are you tackling about.

With the warmest regards,

Katrina

Dear Katrina,

May I ask whom are you talking to? (I'd answer but I'm not sure it was to me)

And by the way I'm very curious about channelling chaos - what do you mean with it?

Best regards,

Maria

chaotic DNA destructions can cause with very small probability (almost zero) activation of preprogrammed-atavistic program.

Lack of oxygen can cause bioenergetic problems, and as a result cancer transformation.

best regards,

Andrzej

Dear Andrzej

Stochasticity and chaos are not identical. Chaotic sequences can be produced by determinate algorithms as first shown by Lorenz.The difference is important because the variations in determinate chaos are constrained by an attractor, whereas genuine stochasticity is not. This property of chaos explain clonal evolution of cancer is initiated by tissue-specific transcriptional requirements .

Best

Dear Mesut,

I have written about "chaotic DNA destructions" - chaotic DNA destructions do not generate chaotic sequences.

regards,

Andrzej

Dear Maria,

Chanelling chaos, pre-determined or tamed chaos - I am not sure that can explain it qualitatively. Here Mezut as I see is profi. I assumed it from some readings long ago, from information theory, from Ilja Prigogine. If you have not read his " Order from chaos" - I recommend very much. You can find it in Russian. Once I did a work on transdifferentiation, where this pre-determined chaos was seen very clearly, it is published but as you are not a biologist, I shall try to explain simply. It was shown that state of cells 1 is changed after trauma into state 2, which is another type of cells, in fact, It occurred through a series of intermediate states, many of them were erroneous (I had a method to estimate this by their production in electron microscope) - chaotic mixture of the product (often found in cancer). It is called amianthoid. And erroneous intermediate cells died but likely also they conditioned (channeled) the nearest environment. A lot of sorting. So, it went through two weeks until the necessary phenotype (state 2) was achieved and all stabilised. But the process was pre-determined by the gradient of the natural inducer causing state 2. Literary, each time as a cell divided in two, the daughter cell which was on the side of this inducer underwent these changes towards state 2, while another daughter usually stayed like their mother. So, it happened - step by step. Likely I sent this article to Mezut. Till now I am impressed by this process. Besides experimental articles, I described it and some other examples in the small review article, please, see attached.

With best wishes, Katrina

Dear Katrina,

Thank you very much for your explanation and for sharing your review. I dealed with theory of chaos but only in DSP (digital signal processing), so this information is new to me.

Best regards,

Maria

One of the implications of the theory of chaos in information transfer ( live dissipative systems are consuming information) may be using of the multiplication of the information carriers (channels) to compensate noise, that is multiplication of the genomes bringing to giant cells characteristic of cancer. In some sense, circulum viciosum because the multiplicated genomes accumulate mistakes (mutations). I do not know if anybody exploited this idea. May be you? It may be right although too abstract.

With kind regards,

Katrina

After chaotic DNA destructions, cancer cells should die - but they are alive.

This can mean that the DNA of cancer cells is still perfectly well organized.

regards,

Andrzej

Dear Katrina,

Thank you, why not? Sounds interesting though I need more information. What could you recommend me to read about this particular idea to begin with?

Best,

Maria

Dear Maria,

I understand your curiosity. The idea was suggested by me 50 years ago, after reading Claude Shannon. It is too general as I think now, although it may be applied to polyploidy (polygenomic nature of cancer cells in response to damage, in particular).

Dear Andrzey, after chaotic desctruction of cancer chromosomes in pieces by chromothripsis, some cancer cells survive. They can do anything.

Unfortunately, our discussion is too amateuric.

Have a nice week-end!

Katrina

Dear Katrina,

Chaotic creation means chaotic result.

BUT - chaotic destruction does not mean that result is chaotic - for this reason I have written that after chaotic DNA destructions "the DNA of cancer cells is still perfectly well organized".

best regards and have a nice weekend,

Andrzej

Dear Andrzej,

I am afraid that our lives are too short to understands these puzzles. May be, we should look for organised order in another place - in electromagnetic waves, acustic waves, electricity associated with DNA and the whole genome - the holistic appearance of life. What is life, besides genetic code?

Best regards, Katrina

Dear Katrina,

What is life? - a good and not easy question.

"You see, life is you and me, this bird, this tree and this flower" (*) - can be this short answer?

best regards, Andrzej

(*) https://lyricstranslate.com/pl/w-życiu-piękne-są-tylko-chwile-only-some-moments-life-are-beautiful.html-0

Dear Colleagues, Dear Maria, Dear Katrina,

The following is an understanding of a mathematician about the modeling of biological systems using modern theory/computational tools of complex systems.

Biomater is fascinating from the mathematical point of view. With a certain simplification, it can be understood as a collection of automatons or agents (representing cells), which carry on their tasks with respect to their surrounding (understand other cells).

Complex system models and theories are built exactly around this idea. You have an ensemble of agents communicating locally, according to some rules. Even very simple rules can lead to very complex responses (see the John Conway's Game of Life in the following publications).

In biology and medicine, it means that regulation of cellular responses can be carried out gradually, in steps, as they accommodate gradually changes in their environments and change their responses accordingly.

The crucial processes in complex systems are containing self-organization and emergent behavior. It is same in biology. Simple systems are capable to build from low-level interactions or virtual entities (called emergents) higher-level entities/emergents. Whenever this hierarchy of emergent, multilayered, multiscale system get disrupted a very chaotic behavior can occur.

I know such pathological behavior from my own research in physics, computer science, mathematics artificial intelligence, and medicine (prediction of arrhythmias from ECG recordings).

Hopefully, you find this information interesting? When you want to know more, there are existing a poster and a review paper that will help you to build knowledge of those processes, and how they are applied in biology and medicine. There are important references for further study of the subject.

I am not a specialist in cancer but while observing cancer behavior, research around it, and discussions, there is present a strong conviction that cancer can be modeled and understood using mathematical apparatus that is being developed in complex systems.

Unluckily, since 2017 I do have some serious health problems that suppressed me from participating in such discussions but now there is some time to fulfill what I promised. You can ask me more questions about the links between complexity and cancer as I feel responsible for those who are ill and waiting for medical progress.

Poster - a brief explanation of complexity in medicine:

https://www.researchgate.net/publication/305751754_COMPLEX_SYSTEMS_AND_THEIR_USE_IN_BIOMEDICAL_RESEARCH_MATHEMATICAL_CONCEPTS_OF_SELF-ORGANIZATION_AND_EMERGENCE

Review paper Complex systems in medicine:

https://www.researchgate.net/publication/330546521_Complex_Systems_and_Their_Use_in_Medicine_Concepts_Methods_and_Bio-Medical_Applications

Dear Jiří,

Very good motivation.

But in what way can we stop this evil? According to my articles, detonation of cancer mitochondria should stop the progression of cancer.

best regards,

Andrzej

Dear Jiří,

First, what is biomater?

Second, there is a great amount of very different ideas about how cancer "can be modeled and understood", and I believe that almost each author is convinced that his particular idea is the right one. To convince the others one has at least to propose the model that can explain the epidemiological data.

Third, I have no idea why Researchgate underlines my writings today, it's not my fault.

Regards,

Maria

Dear Andrej & Maria,

I have read your paper about mitochondria. It is very interesting and deep. There are other theories which I had read in the past about cancer and many, which I definitely do not know.

Before answering how to stop the threat of cancer, a few words about my own disease must be said. I got serious cardiomyopathy after a refusal to treat tonsilitis by my GP while being seventeen. Little did I know that I will go through about 30 heart and heart-related operations, biopsies, and ablations all ended by heart transplantation.

Nothing was helping to get an upper hand above the disease until I started to study and practice holistic approaches of healing and mitigation of serious diseases.

Surprisingly, it was and still is working. What I did discover? That my body of nor just a set of organs that live independent lives. Quite the opposite. I started beside special exercises like walking in a meditative state, and later Yoga & Qigong to explore the influence of diet on my health.

Gradually, it occurred that what I eat and especially do not eat have a great impact on my overall health and even on the heart. Recently, my observations and dietary regimen got confirmed scientifically as a very important part of ourselves - the intestinal microbiome - that can cause almost all civilizations diseases: atherosclerosis, diabetes, metabolic diseases, leaking gut syndrome, RA, autoimmune diseases, Asperger's & autism, anxiety & depression, etc. This all was recently being confirmed by biomedical research.

Here we are. All those diseases are somehow related to either infections or inflammation in situ. We are still far from understanding how it works but we know that healing gut microbiome heals the above-mentioned diseases.

There are two questions. Is it working even for cancer? Some research results already suggest that it works. Then it is worth to explore animal models. It is out of my field of expertise.

The second question, which is in the core of my expertise, is: "Can we build mathematical theories capable to test various hypotheses made above possible mechanisms standing behind cancer?" My answer is positive. We already have mathematical & especially computational tools that are capable to achieve this goal.

My answer is not aimed to mentor anybody or give armchair advances. My answer about what we already are having mathematical tools to define rigorously hypotheses and test them. Undoubtedly, it would be very difficult but simultaneously very exciting and probably can help many ill people to get better and heal.

I do personally do no know enough from experimental data on cancer to be capable to design a good model(s) but know a lot of mathematics. You know a lot about cancer and may be found interesting to cooperate with mathematicians.

This was exactly the main reason to provide the poster and a review paper about a complex system and their applications in medicine (see the previous answer for links). It is possible, I hope that it will happen, then someone while reading those review texts will get an idea how to build complex system model(s) of cancer that can be epidemiological a and biologically tested.

After two months or so there will be some available time to spend on a design of a model with the cooperation with any one or all of you. I feel a great responsibility to those who get this disease. When there is a chance to proceed, we have to try it. I will.

Definition: The term bio-matter is in contrast with the matter. Complex system models of matter have a transition (evolution) function which is fixed. Bio-matter is more tricky and difficult to model as it changes the evolution rules on the fly.

It is very challenging to model biological system exactly because they literally change under our hands.

You can ask more, criticize, discuss. All parts of the discussion are very important on the way of our understanding of diseases and their real causes.

Dear Jiri,

I swear, Andrej and I never wrote any article together :)

Dear Jiri, I am so glad to hear from you again and that you are working. You are right and not right, in my view. One tree is not a forest but a forest can grow from one tree. An organism is composed of many cells with their different functions but they are produced from one fertilised ovum. One cell of the unicellular organism (amoeba) can fulfill many different functions (reproduction, nutrition, defence, motility). One differentiated cell of a multicellular organism can be reprogrammed to the state of embryo. The idea of cellular automata may be applied but it cannot be universal. To understand cancer one should deepen in evolution of life. It is our mutual aim and mutual effort. Good luck and keep in touch! Katrina

Dear Jiří,

Regarding evolution, I have written two articles about it: evolution of normal cells from bacteria to human ("A new approach to the automatic identification of organism evolution using neural networks") and evolution of transformed cells ("Bioenergetics of life, disease and death phenomena").

best regards,

Andrzej

Dear Andrzej,

I should certainly read your evolution articles, can you attach them?

Neural networks is something fascinating - self-learning computer as I understand, is it? It is someting that I can grasp only intuitively, not educated enough. Let us all discuss it after summer holiday!

Dear Katrina,

My articles about evolution with my implementations of the computer programs:

Cancer evolution: https://www.researchgate.net/publication/326302952_Bioenergetics_of_life_disease_and_death_phenomena

Evolution of normal cells from bacteria to human:

https://www.researchgate.net/publication/297895299_A_new_approach_to_the_automatic_identification_of_organism_evolution_using_neural_networks

and also:

https://www.researchgate.net/publication/265042407_Identification_of_Protein_Family_Representatives

https://www.researchgate.net/publication/232041433_A_Novel_Method_of_Sequence_Similarity_Evaluation_in_N-dimensional_Sequence_Space

best wishes,

Andrzej

Dear Andrzej,

These are great articles, elegant work!

Thank you very much.

Katrina

Thank you Dear Katrina,

my small steps to understand all this (life)...

best wishes,

Andrzej