Dear Mesut:

Excellent question

I used to work with a number of very talented physicists who believed that biologist did not have “why gene”!

I have been trying to figure out the basis for “Why Gene". I have been reading on this subject I believe have some good explanations:

The two most important questions in science are:

"What Can I Know?"

"How can I know it?"

Science and religion part ways over the first question. Religion and philosophy believes it can know or at least address the question "why". Of course, the answer ultimately comes down to the way God ordered it. Religion is inherently conservative; even one proposing a new God only creates new order

The question "why" is too deep for Science. Science instead believes it can learn "how" something occurs.

Revolution of modern science and especially medical sciences began as science not only focused on the answers to "what can I know?" but more importantly, changed its method of inquiry, and changed the questions to "how can I know it?"

In a broader context, these questions and answers involve not only simply academic pursuits; it affects how society governs itself. Briefly, the more the society believes in "supreme high" [thus it believes that it knows the truth], is more likely to enforce rigid decrees [like Muslims nations these days].

On the other hand if it leaves room for doubt, it is more likely to be free and open.

In a narrower context of science, the answer determines how individuals explore nature-

o how one does science.

o the way it answers the questions

o One's methodology matters as much as the question. For method of inquiry underlies knowledge and often determines what one discovers

o How one pursues a question often dictates , or at least limit, the answer.

Indeed, methodology matters more than anything else. Methodology subsumes [for example , Thomas Kuhn’s well known theory of how sciences advances]. He gave the word “paradigm” which assumes that at any given point in time, a particular paradigm [a kind of perceived truth], dominates the thinking is science. Thus, prevailing paradigm tends to freeze progress, indirectly creating a mental obstacle to creative ideas. However, scientists who observe “anomalies” that do not fit the paradigm, argue for a new paradigm that explains both old and new facts.

Yet the scientific methods has not been used by those who inquire into nature. Through most of known history of, investigators trying to penetrate nature, penetrate what we call science, relied upon mind alone, reason alone. They believed that they could know a thing if their knowledge followed logically from what they considered a sound premise. In turn they based their premises chiefly on observation

While we can not attribute lack of scientific progress exclusively to religion and superstitions, they contributed to the lack of progress in medicine and biology. The turning point in history was Francis Bacon attacked purely deductive reasoning of logic [Novum Oragnum, 1605]. Logic according to him gave stability to errors which have their foundation on commonly perceived notions!

While Newton [in late 1600] revolutionized physics and mathematics [mathematics is the logic of Physics], John Locke proposed pursuit of knowledge through experimentation.

Biology [life in general] is not a product of logic. The primary driving force of biological systems is evolution. Evolution is predicated upon making the best of available resources [genetic, chemical, environmental etc]. Thus using logic exclusively to pursue may not yield the desired effect.

Let me give one example. In 1796 Benjamin Rush [probably most important physician of the time, signer of declaration of independence] advanced a hypothesis, purely on logic. He believed it as logical and elegant as Newtonian physics. Observing all fevers were associated with flushed skin, he concluded that this was caused by distended capillaries and reasoned that the proximate cause of fever must be ‘abnormal convulsive action” in these vessels. And since capillaries are part of the circulatory system, he proposed to reduce the convulsive action by “depletion”. Thus bleeding the fever patients was generally accepted as a standard practice until recently. Even today the British medical journal keeps its original name “Lancet”

What can I know? How can I know?

If reason alone can solve mathematical problem, if Newton could think his ways through physics, then why could not man reason out ways in which the body worked? Why did reason alone utterly fail in medicine?

The main reason is that evolution is not based on logic, but incremental changes that reflected adaptive changes due to temporal environmental pressures. Life does not choose the most logically best design to meet a new situation. It adapts what already exist. Most of the human genome is highly conserved, which are essentially the same as those much simpler species. Evolution has built on what already exists.

The result, unlike clean straight lines of logic, is often irregular.

This does not mean that logic has never been applied in medicine. The best examples are in “numerical systems” such as statistics to correlate the probability of disease causation, correlation of physical parameters such as temperature, pressure etc to disease state. Now we are slowly converting digital logics in biology..

Thus numerical biology is a recent investigative approach in the USA. We can easily conclude that investigations based on combination of logic, experimental probes and mathematical analysis of data is only 60 years old. The impetus to have numerical approach to biological sciences came from NIH’s focus and funding criteria. A number of scientists decided to start their investigations based on a “working hypothesis”. This was possible because funding for “experts” was already in place. These experts worked on a narrowly focused areas in biology and medicine. This created scientist working their whole life on a single enzyme. Deeper knowledge on various components that make life possible kept accumulating. Specialized research groups started developing “school of thoughts” thus creating research groups instead of individual researchers. While it created volumes of data, there were no impetus for a coherent theory and validation of the same.

Evolutionary selection process that left vestigial components intact also created impediments to clarity on “cause and effect” One such example is the presence of mitochondrial enzymes such as superoxide dismutases. If one has to look for the role of some of these compounds in the cell survival, it will lead no where. In all likelihood, it is a consequence of evolution [symbiotic adaptation of bacteria and eukaryotic cell].

So, who has the “why” gene? And why?

In a perfect Pavlovian conditioning, scientists inquiring physics through mathematics express their “Why” gene. Inquiries into biological sciences through “why questions” often end up in dead-end. One of the reasons for this is the absence of systematic data on complex chemical interactions that constitute life. Thus biologist suppress their “why” gene to pursue inquiries into nature through observations and narrowly focused probes.

Bottom line: In order to fit any biological phenomena into a series of equations, all basic chemical processes will have to be delineated in detail.

“Science is built of facts the way a house is built of bricks, but an accumulation of facts is no more science than a pile of bricks is a house”

H. Poincaré

Dear Ravi

Thanks for yours answer. First of all we must change our reductionistic Newtonian scientefic philosophy.

Second : "What Can I Know?" is not true phrase. We must say "I must know"

Dear Mesut, below is ur answer:

M. Itik and S. P. Banks, Chaos in a three dimensional cancer model. IJBC, 20 (2010) 71-79

Find the paper that u were searching.

Thanks for yours answer. I will contact the aouthors

Dear Belut,

Take a look at this recently published paper in Journal of Theoretical Biology 349, 74-81 (2014).

https://www.researchgate.net/publication/259972930_Avoiding_healthy_cells_extinction_in_a_cancer_model

It deals with the application of a novel control method of chaotic dynamics to a cancer model with transient chaos.

Kind wishes,

Miguel AF Sanjuan

Article Avoiding healthy cells extinction in a cancer model

it's simple, see http://eng.ikar.udm.ru/sb/sb22e.htm,

http://ikar.udm.ru/sb/sb17-4e.htm - Adaptive treatment method (artificial biofield source in medicine);

http://ikar.udm.ru/sb/sb45-3e.htm - Water - a source of biological and electrical energy;

http://ikar.udm.ru/sb/sb38-4e.htm - Non-contact activated infusion solutions as applied to prophylaxis of postoperative pancreatitis of oncopatients;

http://ikar.udm.ru/sb/sb43-3e.htm - The Treating of Patients in U.S.A. using Anolyte, Catholyte and Non-Contact Activated Liquid (NAL);

http://ikar.udm.ru/sb/sb46-1e.htm - Open seminar professor Ashot Khachatryan in Singapore;

http://www.ikar.udm.ru/pr-1.htm - Non-contact activation of liquids (infusion solutions and drugs, drinks, tea, coffee, drinking water, including tubs, swimming pools, an intensification of biotechnology, the extension of the deadline life);

Here is my opinion

Opinion

I described epithelium as a system, stem cell as active adaptive agent and stem cell genome behavior as an agent’s behavior

1. Ordered behavior: Stem cell has capacities for self-renewal and for asymmetric division leading to generation of epithelial differentiated cells (progenies). The differentiated epithelial cells have to be faithfully maintained to provide a secure barrier and guarantee the body’s homeostasis. This is achieved by the constant replacement of exhausted cells with newly formed healthy progeny originating from the stem cells. In many tissues, stem cells are thought to reside within a niche formed by a group of surrounding cells and their extracellular matrix, which provides an optimal environment for stem cell homeostasis.

The environment around differentiated cell fluctuates regularly and predictably under physiological conditions. The flexibility of stem cell allows to differentiated cells (progeny) to deal with their constantly fluctuating environment. Aging , unpredictable ,previously genetically unknown (such as radiation, new chemicals etc.), weaken the normal function of differentiated cells. Declining functionality is paralleled by diminishing capacity to respond to microenvironmental injury or stress .

2.Edge of Chaos: Stem cells can change flexibly according to the environment, while differentiated cells have no such flexibility. Stem cell provide the previously- known, another type of resistant differentiated cells for the protection of epithelial system (transition of epithelium another type of epithelium :such as Barret esophagus, ductal or lobular hyperplasia of breast) or re-organized architecture of epithelium (colo-rectal polyps, gastric polyps etc.)At this state, the system is optimized for adaptation to stressed microenvironment. In this state system is predictable and controllable.

3. Chaotic behavior: When, microenvironmental stress persists and new epithelial cells continue to die, system gone into a crisis. The crisis causes a series of changes which result in the renewal of the adaptability structure. The stem cell genome jumps to chaotic state for adaptation. Chaotic behavior of the stem cell allows to production of new stress resistant and previously unknown progenies(cancer cells) or atavistic cells(metazoan 1.0). Since this stochastic'' behavior is generated by a deterministic chaotic mechanism. Clinically this state represent as local advanced or metastatic carcinomas. Presences of mutated tumor suppressor and/or genes onco-genes facilitate chaotic behavior. Genome chaos acts as a mechanism of rapid, adaptive, genome-based evolution that plays an essential role in promoting rapid macroevolution of new genome-defined systems during crisis. This is consistent with experimental observations that genome chaos, a process of complex, rapid genome re-organization.

With regard to biological systems, chaos might be better considered as entropy (i.e. disorder), and as a biological system grows each new cell (or “agent” or “node” when considered as a multi-agent complex adaptive system) carries with it an amount of entropy. In Per Bok’s sand pile simulations of entropy, each grain of sand that piled up added entropy to the system until the system experienced a collapse, but biological systems do not collapse because they somehow manage to deal with that increasing entropy. Theoretically that entropy can be reduced via non-trivial quantum mechanical processes (i.e. quantum logic).

(http://arxiv-web3.library.cornell.edu/abs/1208.5729v1)

Many have speculated that the disorder/entropy of cancer seems related to a loss of quantum coherence in a biological system, but the problem has been that there has heretofore been no viable model of how such quantum coherence could be maintained in a biological system. I have put forth a model of how quantum logic takes place within the DNA of a biological system that has implications for the quantum coherence of an entire biological system.

(http://www.mdpi.com/2075-1729/3/3/474)

So the chaos that is being considered might better be thought of as entropy, and the adaptive “genome jumps” (Schrödinger used the term “quantum leaps” in his book entitled What is Life?) might better be thought of as quantum walks. Also, what is being considered as a “deterministic chaotic mechanism” might better be thought of as the deterministic output of a DNA quantum mechanical Turing machine (that I describe in a recent paper entitled “Implications of the Landauer limit for quantum logic”).

(http://proceedings.spiedigitallibrary.org/proceeding.aspx?articleid=1876253)

It has been disappointing that we still have no significant understanding of what “cancer” is, and I believe that such understanding will come from an understanding of the non-trivial quantum mechanical processes that maintain order in biological systems.

Most probably if the initial condition is an oncogene activating muatation or tumor suppressor inhibiting mutation, the downstream effects of these mutations will depend on cellular milieu  for the mutation effect to take place-sensitive dependence on initial conditions