Theoretical Biology and Medical Modelling - Latest Comments

Fit parameters for RECTUM

Uwe Schneider — 2012-03-23T18:02:55Z

Dear Reader,
Upon the publication of the manuscript titled ¿Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy,¿ it was found that EAR for Rectum from the Dores data was obtained (for agex=30 and agea=70) by using the temporal patterns of ¿all solid cancers¿ (parameters¿ game = -0.024 and gamaa = 2.38). However, it would be more realistic to use the temporal patterns for ¿Colon¿ (parameters¿ game = -0.056 and gamaa = 6.9). A re-calculation of EAR for ¿rectum¿ resulted in 12.5 instead of 1.53. As a consequence the EAR model fitted the ¿rectum¿ data with the following results:
- Linear model: not converging
- Full model: alpha=0.033, R=0.56, CV=2.4E-5
- Bell shape: alpha=0.031, R=0, CV=1.9E-3
- Full recovery: alpha=0.065, R=1, CV=7.5E-4

We are sorry that this error was not observed at an earlier stage.
Best regards,
Uwe Schneider

Excellent paper

David L. Abel — 2011-06-11T20:01:17Z

This paper provides an invaluable critique of the capabilities of Avida to spontaneously evolve sophisticated new Prescriptive Information (PI), bona fide organization (as opposed to mere low-informational physicodynamic self-ordering), and ever-increasing higher formal function. The role of "investigator involvement" and artificial selection must be taken into account when programming cybernetic models of supposedly natural phenomena. Inherent human steering is often hidden in the experimental design. The application of sound population genetics principles to such models also sheds new light on their much touted creative capabilities.

Thermodynamics and fractality - not enough in an electromagnetic world

Gregory O'Kelly — 2011-05-26T19:59:36Z

Dr. Kurakin states, "...how exactly the apparent decrease of entropy on the planet earth is compensated by an increase in entropy somewhere else is less clear....'somewhere else' can potentially include the whole Universe..." The lack of clarity results from the inclusion of the whole universe rather than planetary or local considerations, at which clarity is more detectible. Yet this is the foundation for the universality of the discovery method he terms "self-organizing fractal theory." He writes, "...the Universe evolves from simplicity and disorder to complexity and order via self-organization, in accordance with the empirical laws of nonequilibrium thermodamics (NET)," and "...self-organizaing fractal theory (SOFT)...(which) implies the existence of universal principles governing self-organizational dynamics in a scale-invariant manner."

He does not say what these implied universal principles of nonequilibrium self-organization are, though he gives a few examples relating to the conduction of heat. These examples, e.g., Benard instability, do not escape the realm of 'classical mechanics and equilibrium thermodynamics that Dr. Kurakin insists comprises classical mechanics, despite the phase changes. Nonequilibrium thermodynamics, as well as equilibrium thermodynamics, does not extend to the world of electromagnetism. Neither is capable of field theory, a key ingredient of electromagnetism. Yet Dr. Kurakin states: (1) "...it appears that the physicochemical properties of proteins have carefully tailored by evolution to support electron transport through proteins and multi-protein complexes"; (2) "...a large body of experimental evidence demonstrates that proteins, nucleic acids, lipids and their complexes represent structured macromolecular media that enable and facilitate the capture and directed transport of electrons and protons..."; (3) "Because so many physicochemical properties of proteins, nucleic acids, and lipids appear to have been carefully tailored by evolution to satisfy the requirements of organized electron transport over large molecular distance, it is reasonable to suggest that electron flow may represent a fundamental physical force that sustains, drives, and informs all biological oranization and dynamics"; and (4) "What appears to be always and everywhere present is a continuous and rapid flow of electrons and protons through each and every living organism." This is the province of field theory, not thermodynamics or statistical mechanics, about which Dr. Kurakin has little to say.

Nevertheless, Dr. Kurakin writes, "Whether explicitly stated or tacitly implied, the phenomena studied in molecular and cell biology are traditionally interpreted and rationalized within the conceptual framework of classical physics, i.e., classical mechanics and equilibrium thermodynamics....despite the commonly accepted fact that the cell/organism (any living organization, in fact) is an open nonequilibrium system, which exists and functions only because of the incessant flow of energy/matter passing through it." That energy is not mechanical or heat energy, but is instead chemical energy, coulombs carried by electrons.

Ludwig Von Bertallanfy [Science, 1951, "The theory of open systems in physics and biology"], the founder of systems theory, wrote that non-equilibrium or open systems self-organize around a steady-state dependent upon their degree of openness. Systems theory is about thermodynamics, and reveals nothing in particular about the nature of self-organizing tendencies of open systems, unless supplemented by electrochemical considerations. Those considerations, as they occur in the allometric scaling of metabolism, are scale invariant. Bertallanfy defines metabolism as the total of the chemical processes involved in energy equilibration needed to maintain a non-equilibrium steady-state, regardless of complexity of the system. In other words the system is always moving toward equilibrium, but its openness allows it to maintain a steady-state short of it. Variations in openness influence the size, growth, development, replication, and organization of the structure. In other words the structure itself is proceeded by the chemical processes that result in it rather than determining what processes might be possible given an accidentally assembled structure.

In the allometric scaling of metabolism openness is expressed as a variable in the exponent of the biomass. Because openness is an electrochemical consideration, it is expressed as a ratio of amperes of anabolism to amperes of catabolism, where metabolic rate is expressed in watts, the power necessary to maintain the biomass short of equilibrium. This is called metabolic efficiency, where the denominator annunciates degree of openness (always changing); and the numerator gages the rate at which the open system is able to harness this openness. In his 2009 on the importance of non-equilibrium considerations in understanding life, Dr. Kurakin held that the version of Kleiber's Law favored by quarter-power scalers like Enquist and West, was seminal. This version does not include any considerations of openness, of metabolic efficiency. Dr. Kurakin does not discuss the power of quarter-power scaling in this latest attempt to account for electron flow in terms of thermodynamics.

Dr. Kurakin notes "...degree of order and the rate of energy/matter flow are co-defining in far-from-equilibrium systems, large-scale conductivity is an emergent property of organization (an ordered whole) rather than of component parts. Properties of parts are only compatible with and, in fact, are often selected and/or reinforced by the emergent properties of the organizational whole." This phenomenon is expressed in allometric scaling by the value for metabolic efficiency (the variable in the exponent of biomass annunciating degree of openness of the system) being determined by the whole and applying to all the parts. Large-scale conductivity is seen in the development of nerves and the nervous system.

Dr. Kurakin speaks of an 'electron gradient' as a key force (or pressure) driving electron flow. This pressure is voltage, electrical voltage, not entropic pressure resulting from gradients of particle concentration, the standard model of bioelectricity that treats thermodynamics and electromagnetism as commensurable and mutually substitutable, as Peter Mitchell, Alan Hodgkin, Andrew Huxley, and John Eccles believed. Dr. Kurakin suggests electron transfer is related to the flux of charge and matter. This explanation embodies two properties of batteries. In the first case the battery is a rechargeable battery able to capture, because of a voltage pressure, an electrical field, in the reversal of a catabolic chemical reaction within. This is in essence the generation of negative entropy.
This is how life started.

In the second case, that of matter, the battery is non-rechargeable, and must have new chemicals introduced that may, in turn, be catabolized for energy content, as in digestion or any form of heterotrophism. In the first case we have a secondary cell, and in the second case we have a primary cell, two different types of batteries. The aggregation of secondary cells driven by fluctuations in metabolic efficiency resulted in the evolution of biomass that had primary cell capabilities. These capabilities were at first limited to the effectiveness of the tidal flow of water bearing nutrients, and later occurred as stomachs with capillary delivery of substance to the individual cells and organelles of the emerging structure. At this point the fractality Dr. Kurakin holds dear may have had some influence on the evolution of the structure. But such fractality does not extend to attempts to understand the origins of life. Only appeal to secondary cells can do that. In other words fractality might have something to do the equilibration of energy flux through the organism (as it concerns movement of matter for strictly local catabolic breakdown), but reveals little pertinent to the forces and pressures behind the origins of life and self-organization of the organism. These things can only be understood in terms of thermodynamics and electromagnetism as they act upon aggregations of organic molecules.

BKMin, Ramon-y-Cajal and Pierre Janet

Paul Brown — 2011-05-25T10:37:04Z

BK Min’s interesting article, ‘A thalamic reticular networking model of consciousness’ (Theor Biol Med Model, 2010; 7: 10) advances a model of consciousness that has its roots in the work of Ramon y Cajal. It is fascinating to speculate how the face of neuropsychiatry might have advanced, if Cajal had exchanged ideas with his French contemporary, the psychiatrist Pierre Janet! For at the same time that Cajal was making his wide-ranging neuro-anatomical discoveries, Janet was making comparable discoveries in the phenomenology, and psychopathology of consciousness. Essentially, Janet contemporaneously developed a synthesis-dissociation model of consciousness without suggesting its possible neuroanatomical basis.

Janet, some five years Cajal’s junior, qualified in medicine a decade- and-a-half later, in Paris. They shared an involvement with ancient universities, yet in every other way one could not imagine two more distinct milieux. It was Ramón y Cajal who crossed the frontier between Spain and France; we have no evidence that Janet did so. Cajal became a corresponding member of the Society of Biology of Paris (1887). Cajàl was awarded the Fauvelle Prize of 1,500 francs of the Society of Biology of Paris (1896). The Moscow Prize of 5,000 francs, established by the Congress of Moscow (1897) to reward medical works which, published during the latter three years, have rendered the greatest services to science and humanity was awarded to Ramon y Cajàl by the International Congress of Medicine in Paris (1900). In 1906 he was elected an Associate Member of the Academy of Medicine, Paris. During that period, Janet was working at the Salpétrière, first under the neurologist, Charcot, and then under his successor, Raymond. Yet we have no evidence that Janet and Cajal ever met, and there is no reference to Cajal in Janet’s oeuvre. That is a pity, because Cajal’s concepts of the thalamo-cortical basis of consciousness would have wedded readily with Janet’s.

In my own explorations into the neuroanatomical basis of consciousness, I find it useful to link consciousness with the agency and identity of the self. I hypothesize that thalamic substrates are responsible for switches between states of consciousness and corresponding self states, while cortical substrates are responsible for the finer variations of consciousness within each of those self states. The basal ganglia regulate self states via mechanisms of reinforcement, and the brainstem regulates levels of consciousness in the waking-sleep cycle. The cerebellum is the temporal modulator alongside these scalar controls, namely cortical, thalamic, basal ganglia and brainstem. I believe that the next step is to link anatomical studies with those of Janet and his present day neuropsychiatric successors.

Yours Sincerely,
Dr Paul Brown
Director
The Pierre Janet Centre
Kfar Vradim, Israel

Competing interests
None

Minor errata in Theoretical Biology and Medical Modelling 2010, 7:31

Paul Agutter — 2010-08-24T19:39:16Z

Despite proof-reading of the final manuscript, some errors crept through into the published PDF. None of these errors materially affects the argument of the paper, but we apologize for them nevertheless. We list them below.

Abstract
“Additionally, an FPE rate of about 0.012% (35/28,400) in patients receiving prophylactic anticoagulants…” should read “Additionally, an FPE rate of about 0.12% (35/28,400) in patients receiving prophylactic anticoagulants…”

Main text
Under Statistical considerations in designing non-inferiority trials, “The occurrence or non-occurrence of each safety and efficacy endpoint within the stated follow-up interval will be recorded. Potential confounders (subject age, gender, medical history, type and severity illness, type and duration of surgery, etc.) will also be recorded...” should read “The occurrence or non-occurrence of each safety and efficacy endpoint within the stated follow-up interval will be recorded. Potential confounders (subject age, gender, medical history, type and severity of illness, type and duration of surgery, etc.) will also be recorded...”

Tables
Table 1 contains a redundant reference, and this redundancy slightly affected the totals. The first line of the table under "author" should read Mahé [89, 92]. The totals should read: 489 / 12,367 (4.0%); 443 / 12,629 (3.5%)

Table 2: The closing parenthesis after ‘patients’ should be dropped.

Table 6: the hyphenations in Arm-strong and Tungtrong-chitr should be eliminated.

References
Cochrane apparently took down direct access to their review abstracts, so the URLs in the references need to be amended:
#20 Change first URL from the Cochrane website to PubMed: http://www.ncbi.nlm.nih.gov/pubmed/16437461
# 87 Change URL from the Cochrane website to PubMed: http://www.ncbi.nlm.nih.gov/pubmed/19588346
#91 Change URL from the Cochrane website to PubMed:
http://www.ncbi.nlm.nih.gov/pubmed
#95 Change URL from the Cochrane website to PubMed:
http://www.ncbi.nlm.nih.gov/pubmed
#98 Change URL from the Cochrane website to PubMed: http://www.ncbi.nlm.nih.gov/pubmed/19160234
#110 Change URL from the Cochrane website to PubMed: http://www.ncbi.nlm.nih.gov/pubmed/18843687

David K Cundiff, Paul S Agutter, P Colm Malone and John C Pezzullo

Trial of Anticoagulants vs diet in DVT prophylaxis

Stefano Ricci — 2010-08-23T22:21:00Z

The idead is interesting. However, taking into account the widespread use of AC prophylaxis, I think that diet measures should be firstly used against standard care (and no AC) in patients who cannot be treated with AC (i.e. haemorrhagic stroke, contraindications to AC, etc). If diet measures reveal some effect, than a trial vs AC can be organised.

A more general approach predates this report.

Rui Alves — 2010-04-13T15:14:11Z

I believe that there are more general approaches that deal with the issues discussed in this paper. The approach reported here has a serious shortcoming in dealing, for example, with sigmoidal saturation. Given that approximation theory, e.g. through Taylor series, can be used to create generic equations that describe the full class of biological saturation phenomena, what do we gain from going back to a less general formulation?
For example, as far as I can tell, Sorribas et al (Biotechnology and Bioengineering Volume 97 Issue 5, Pages 1259 - 1277) have already proposed a formalism that deals with the issues address in this paper. That work is based on earlier work by Savageau (Savageau, M. A. (1976). "Biochemical Systems Analysis: A Study of Function and Design in Molecular Biology," Addison-Wesley, Reading, Mass.)

Llinas; epistemic gap

Steven Ravett Brown — 2010-04-03T10:34:24Z

First, this is an old, old, hypothesis. I'm disappointed not to see a single citation or mention of Llinas, who was one of the first to propose it, and who investigated it quite thoroughly (And largely unconvincingly. See my third comment. Llinas never resolved this, although he was aware of the issue.).

Second, to call consciousness a "mental" state which is capable of "awareness", where the latter is a "mental" state which is "conscious" is egregious and vicious circularity. If you can't define it, why try? Just say you can't.

Third, the author is evidently unfamiliar with or does not understand the "epistemic gap" (Levine's term) or so-called "hard problem" (a more casual label). This is central to any issue regarding consciousness, and was not even mentioned in this paper. If the author is not concerned with it, that should at least be stated. It's perfectly valid to say that the paper is concerned only with behavioral testing of a particular neural hypothesis related to conscious states, but in a paper which claims to set out a "model of consciousness", one should at least nod to this issue.

Cancer proliferation and quantum metabolism

Mark Henderson — 2010-02-13T23:08:30Z

Demetrius et al. [1] have re-investigated Warburg’s metabolic hypothesis of cancer origins in terms of quantum metabolism. Their paper seems timely because, as the authors note, there has been renewed interest in the Warburg hypothesis during recent years. Whether their interpretation will prove useful remains to be seen, but it should interest workers in the field.

My colleagues and I were therefore surprised by the comment from O’Kelly [2], which seeks to dismiss the proposals of Demetrius et al. [1] on grounds best described as dubious. O’Kelly appears to claim acquaintance with previous publications by Demetrius, but in his first paragraph he states that he does not understand the phrase ‘the methodology of quantum mechanics’. Yet it is clear, e.g. in [3], that quantum metabolism exploits Debye’s quantum theory of solids, using the same mathematical approach as Debye. Surely that is not a difficult idea? Later in the comment, O’Kelly tells us that ‘quanta’ have nothing to do with proton pumps but are ‘energy states of the electron… as discrete as different wavelengths of photons’. Physicists will find those remarks oddly worded, to say the least, but in any case they are irrelevant to quantum metabolism, which is not at all the same as quantum mechanics – it simply uses the same mathematical apparatus as Debye’s theory.

In the first paragraph of his comment, O’Kelly also identifies three definitions of ‘metabolic efficiency’ used in [1] and implies that they are incompatible; in fact, as anyone familiar with cellular metabolism will recognize, they are essentially equivalent. Later, he claims that ‘metabolic rate’ is used in several inconsistent ways in [1], but once again these ‘several ways’ are essentially the same, as any competent biochemistry undergraduate would know. O’Kelly’s suggestions that Demetrius et al. ‘reveal their lack of familiarity with the term (quanta)’ and ‘ability to appreciate [the Kleiber equation’s] power was limited… by failure to understand the quantum nature of chemical energy’ therefore appear ironic.

His comment [2] contains other curious statements. For example, we are told that a phosphorylation potential is not a form of energy; in other words, the chemiosmotic hypothesis (which is accepted by the overwhelming majority of biologists, including Demetrius [3]) is false. Proportionality constants can apparently be neither measured nor calculated but are ‘disembodied hypotheses’, an assertion that will no doubt alarm mathematicians throughout the world. And O’Kelly is unable to accept that fermentation and respiration involve different types of energy coupling, thus requiring every elementary biochemistry textbook to be rewritten and Pasteur’s classic experiments to be re-investigated.

The proposals of Demetrius et al. [1] are speculative and deserve critical scrutiny, but any such scrutiny needs to be based on a better understanding of basic science than is apparent in [2].

References

1. Demetrius LA, Coy JF, Tuszinsky JA: Cancer proliferation and therapy: the Warburg effect and quantum metabolism. Theor Biol Med Model 2010, 7:2.

2. O’Kelly G: Quantum metabolism and cancer – power in numbers. Theor Biol Med Model 7:2 comment.

3. Demetrius LA: The origin of allometric scaling laws in biology. J Theor Biol 243:455-467.

Quantum metabolism and cancer - power in numbers

Gregory O'Kelly — 2010-02-11T17:25:29Z

The authors describe quantum metabolism as 'an analytic theory of metabolic regulation which exploits the methodology of quantum mechanics to derive allometric rule relating cellular metabolic rate (MR) and cell size." I have no idea what quantum methodology is, or how it differs from scientific methodology. But the allometric scaling rule relating MR and cell mass, as proffered by Dr. Demetrius in his 2004 Journal of Gerontology article, has little if anything to do with quantum mechanics, whatever its alleged methodology. And what little it does have to do, relates to the nature of electrical charge transferred in the redox coupling necessary for the creation of covalent bonds. In fact Dr. Demetrius defines metabolic efficiency (ME) there as a ratio of amperes to amperes. In contrast, in this paper, the authors define ME as:
1. "Metabolic efficiency is the amount of ATP produced per unit of substrate material."
2. "The ratio of the energy stored in the various bio-molecules to the free energy released in redox reactions is the efficiency of the metabolic process, which can be as high as about 95%..."
3. "Metabolic efficiency is the amount of ATP produced per unit of substrate material."

Does ME differ from the efficiency of the metabolic process, where the former is an amount, or an amount/unit of substrate, and the latter is a ratio? There is a good deal of looseness to these formulations.

The authors make the claim that OxPhos has a higher metabolic efficiency (chose the definition), and thus a higher MR. This conflicts drastically with the Eq. (1) in Dr. Demetrius's 2004 which clearly indicates that for things of mass less than one gram in size, higher ME means lower MR. Problems loom. The authors also claim: "An increased metabolic rate entails an increased efficiency in the acquisition of resources. Hence, when limited resource conditions prevail, types with higher metabolic rates will be favoured," at a time when Demetrius's 2004 clearly shows that higher MR is something determined by the resources and the ability to use them (ME), and not something that exists independently of those resources.

That same math also clearly shows, contra the authors' claim that "Cancer cells may be considered as autonomous units which have an impared capacity to maintain the metabolic stability of the organism in which they reside," and "...one cell type replaces a related cell type by natural selection," that all cells share the ME of the host, and that this is the nature of biological organization. The authors seem to think the cells of an organism are instead in competition for energy resources such that ME may vary from once cell to another. And to this Darwinian competition are introduced 'adaptive mechanisms', 'regulatory interventions', and 'anti-tumour defenses', none of which appear in the math.

Examination of the definition of MR reveals MR is:
1. Rate of ATP production, and/or
2. "...the totality of chemical reactions in cells carried out by an organism," and/or
3. "...the rate at which an organism transforms nutrients into thermal energy and biological work", and/or
4. "Metabolic rate is the rate of ATP production per unit time..." [surely a redundancy], and/or
5. "... the minimum rate at which the cell uses energy to stay alive," and/or
6. "... determined by the proton conductance and the proton potential of the metabolic system...regulated by the phospholipid composition of the mitochondrial membrane...[that is modifiable by] exercise and diet." The authors don't say how the cells exercise but, instead, seamlessly move between basal and field metabolic rate, and fail to disclose at what scale Darwinian competition for energy is replaced by cooperation of the parts of the organism.

But this is not enough. In matters of ME, "...the transformation of nutrients into thermal energy and biological work involves the inter-converson of two forms of energy: the redox potential difference...[and] the phosphorylation potential..." Redox potentials and phosphorylation potentials are not forms of energy. Energy, chemical energy, is expressed in coulombs or amperes, not volts. Amperes are not potentials. The authors assert that thermogenesis is part of metabolism, which conflicts with the idea "Metabolic efficiency is the amount of ATP produced per unit of substrate material." Only when thermogenesis is considered part of metabolism do we find extremely high efficiencies like that the authors claim characterizes the Krebs Cycle - 95%, an efficiency rating characteristic, at best, of mechanical linkages.

The authors speak of "two classes of metabolic pathways" - fermentation and respiration - where those two things characterize different 'mode of coupling - chemical and electrical, as if electrochemistry did not include both, at a time when redox coupling efficiency (ME) is a term from electrochemistry. They make this distinction repeatedly through the paper, e.g., MR is "determined by the proton conductance and the proton potential of the metabolic system"; "In OxPhos, the coupling is electrical...In glycolysis, the coupling is chemical..."; "The coupling between the electron transport chain and ADP phosphorylation is generated by the flow of protons across the biomembrane"; "In OxPhos coupling is achieved by a single common intermediate between the oxidation of a variety of substrates and ATP formation. The intermediate is the trans-membrane proton gradient"; "All living systems exist in a steady state relatively far from thermodynamic equilibrium and this state is maintained by sustaining non-equilibrium concentration gradients across membranes"; and "The metabolic rate of normal cells is primarily determined by the proton conductance and the proton potential of the metabolic system."

What is problematic with this view of energy is its complete un-relatedness to the quanta of metabolism. Proton gradients, proton pumps, proton conductance, etc., have absolutely nothing to do with quanta. Quanta are the energy states of the electron. They are as discrete as different wavelengths of photons. Use of the word in the favored phrase 'quantum metabolism', in the manner favored by the authors, merely reveals their lack of familiarity with the term. There is a long history to this bit of insular elision that dates to 1902 and Julius Bernstein who sought to explain the electromagnetism of the nervous system in terms of thermodynamics. Bernstein turned to the Nernst equation, a thermodynamic equation of Walter Nernst that spoke of 'elementary particles'. These elementary particles could be any particles in solution or in an ideal gas, i.e., they could be ions, protons, electrons, molecules, whatever. The volts of Nernst were units of osmotic pressure, and had nothing to do with electromagnetism. The claim that there are two modes of energy transduction, one chemical and one electrical, is spurious, because all chemical energy transduction is electrochemical, not osmotic.

"Quantum Metabolism predicts that the metabolic rate of cells utilizing OxPhos and cells utilizing glycolysis will have the same scaling exponents but will differ in terms of the proportionality constants"; and "Quantum metabolism, a new bio-energetic theory of metabolic regulation in cells [dating to 1902], shows the proportionality constants in the scaling laws for metabolic rates of cells utilizing OxPhos and glycolysis pathways are contingent on the different modes of coupling..."

The proportionality constant depends upon the difference in redox coupling modes (ME), a difference obviated when the quantum world replaces the world of thermodynamic electricity, so that the two modes collapse into one. Proportionality constants are not measured, nor are they calculated. They are disembodied hypotheses meant to rescue a tortured scheme. At the same time when MR is determined entirely by scaling exponents (Demetrius 2004), the authors propose "The evolutionary argument rests on differences in the MR of cells utilizing OxPhos and glycolytic pathways, respectively," Demetrius's 2004 shows that when scaling exponents for cells are the same and there is a difference in MR, the difference is due to the mass of the cell, nothing else. The scaling exponents differ if and only if the value for ME differs from one cell to another, something not likely when ME is determined by the organism, and not the cells which comprise it.

The authors are now proposing 'non-invasive' 'regulatory interventions on the basis of quantum metabolism' 'to combat cancer.' "The hypothesis, in its simplest form, asserts that cancer is primarily a disease of metabolic dysregulation..." "...therapeutic strategies based on arresting the transition from normal... to... malignant...may be effective in complementing traditional methods..." Typically, the authors specify no such interventions outside of hints at drugs and pharmaceuticals that might be complementary. They hope to influence MR this way at a time when Demetrius's 2004 shows MR is dependent entirely upon biomass and ME. Presumably ME can be varied for the cell with adequately targeted drugs that act upon modes of energy processing.

Demetrius's 2004, which also supports the hypothesis of cancer as due to metabolic dysregulation, does not stoop to this, the idea of modes of energy processing. Instead of hypothesizing regulatory interventions that might complement traditional methods however, the mathematics suggest the traditional methods target the cell but not the cause of the mutation, a matter of ME, and should be rejected outright. The curves suggest the way to act upon MR is to manipulate ME through the application of electrochemistry. The curves model how the cause of mutation is increased ME from the reduced denominator of its redox coupling ratio, and how this drives cells, whose MRs are collapsing, to degenerate by alternately reducing the numerator of the ratio. This allows the cell to survive in an organism of high ME, which the cell shares. John Cairnes called this 'starvation induced mutation'.

I will always be disappointed Dr. Demetrius never looked into this equation more thoroughly, but I understand his ability to appreciate its power was limited by his understanding of the quantum nature of chemical energy, and how this understanding's electrophysiology was formulated before the quantum revolution.