Stedman's medical dictionary defines iatrogenic :  An unfavorable response to medical or surgical treatment, induced by the treatment itself (1). We shall be less concerned  with iatrogenic consequences of mistreatment, rather with  iatrogenic theories which lead to mistreatment, and  how important biological theories become iatrogenic.

Four principles

Our organism is an open system which obeys four principles. The first three are:
1. It is (extremely) complex.
2. Fully connected.
3. Self-organizing.

'Fully connected
' means that all components interact. The major communication channel between cells is the extra-cellular fluid, carrying hormones, factors, vitamins, etc. Then comes the vascular system.  Finally the nervous system, which carries  two kinds of message. Electrical signals are distributed along axon surfaces , and trophic factors are carried as  axoplasmic flow.  Actually all cells produce electrical signals which originate in cell membranes.  In epithelia they are distributed through gap junctions. Electrical signals  are conspicuous in the heart (sinus node), and intestines (myenteric plexus).These examples ought to convince the reader that all constituents of the body interact.

The ability of the organism to organize itself is called here Wisdom of the Body (WOB) .  In order to understand how WOB operates we need a simpler representation of the organism, and define a unit, called process. It  might be regarded as stream of matter. Or a channel through which products stream. It is directed in space (and time), and has inputs (other processes) and an output (another process).  The three principles become now:

1. WOB is the set of processes in the body.
2. All processes interact (WOB is fully connected).
3. Processes are self-organizing.

At each instance WOB controls processes so as to minimize expenditure of resources. At each instant WOB configuration is the best under circumstances, which introduces the fourth principle:

4. WOB (configuration) is optimal.

Indeterminacy Principle of Biology

When challenged, WOB  reshuffles processes so as to minimize resource expenditure. This configuration is called a solution, which  always settles at an equilibrium, or strange attractor (homeostasis, homeorhesis).  Since processes interact , it is impossible to study a process in isolation. When studying  a process we have to consider also its 'neighbors', which is defined here as process context. Our inability to capture phenomena in their entirety should be regarded as the indeterminacy principle of biology. 

The Central Dogma of Molecular Biology


The dogma was formulated by Francis Crick, namely, that information flows from DNA to RNA  to protein, but does not flow backward. Actually the dogma applies to experiments done in vitro, which is also the proper context in which it is valid. However, medicine applies it also to the (fully connected) organism, where everything flows only forward, and nothing flows backward. In other words, in the organism concepts like forward and backward are meaningless. 'Flowing backwards' is a linear concept adequate for the narrow context of in vitro experiments. In the non-linear WOB forward flowing molecules (proteins) reach anything, even the DNA.

This reasoning illustrates a common fallacy in biology, called here 'context fallacy'. A theory valid in a narrow context is applied (extrapolated) to a different context, where it violates the connectivity principle.  And this context fallacy is iatrogenic since suggesting treatment. Cancer is believed to originate in a defective DNA, and molecular biologists propose to repair it, or even to replace it with a better one.



The central fable of genetics

"Genetics is the science of inheritance. It attempts to explain the differences and similarities between related organisms and the ways in which characters are passed from parents to their offspring" (2). Actually genetics studies only inheritance by genes, and ignores other forms of inheritance. It is founded on the work of  Gregor Mendel, who, in 1865, discovered two modes of inheritance which are regarded as "basic law" of inheritance. Unfortunately, also  medicine regards Mendel's discovery as a law, which has  grave iatrogenic consequences.

Mendel's "laws" are yet another
context fallacy. What medicine takes as a law, is a simplistic model adequate for describing inheritance in peas. It fails when applied to our organism, and to animal populations. In order to cover up for the shortcoming of the model, Mendel and his followers apply a simple trick. They manipulate variability. A closer inspection of Mendel's experiments reveals that not in all peas  inheritance  followed Mendel's "laws" . Mendel and his followers attribute this discrepancy to the act of chance, which  should vanish as the number of observations rises. Like in the normal (Gaussian) distribution. In medicine however nothing is distributed  normally. All distributions are skewed. Yet genetics boldly 'normalizes' distributions and facts, and so spreads iatrogenesis.

Mendel's model requires that a gene be completely isolated. A fixed and unalterable entity. Otherwise the model fails. Anything that directly influences the gene is brushed off as Lamarckian nonsense . The isolated "deaf" gene is the central fable of genetics, which produced some exciting fiction, e.g., "The Selfish Gene", and Neo-Darwinism .

This fable dominates somatic cell genetics, which postulates that  cells in the organism carry isolated and fixed genes,  protected from the influence of outside processes. Since made of DNA, nothing can touch them, as the central dogma postulates. Only chance, manifested by an accidental mutation can change a gene, initiating a fateful disease, cancer. 

All this is supposed to occur in a fully connected streaming organism.

Darwinian nonsense

Treatments suggested by this fable cause unnecessary suffering to patients.
Cancer  supposedly starts when a gene is randomly mutated, which endows it with a survival advantage in the "hostile environment" of the organism. The "hostile environment" is none other than the  immune system, the Grand Protector of our Self, which attempts to kill the outcast (with nk-cells). Yet the "evil clone" continues to mutate, and gains in strength. Tumor evolution recapitulates Darwin's evolution of the species. Clones of cells with new mutations reproduce faster and faster, grow, spread and finally kill the patient. 

This horrible fable shapes cancer treatment:  "Cut out the clone before it spreads. Otherwise poison its progeny."

One wonders, if indeed such a course shaped  the evolution of humankind,  why do we still carry these potential killers? Why weren't they "selected out" earlier in our evolution?  Something in the "survival of the fittest" notion stinks. Or perhaps humankind survived because of neoplasia?

Philadelphia chromosome

The central dogma and the genetic fable dictates how cancer should be interpreted. An evolution brought about by chance mutations.  Like in the  Philadelphia chromosome, which is believed to cause  chronic myelocytic leukemia. The mutated gene produces a  fusion protein which supposedly transforms white cells into malignant , and ought therefore be silenced by anti-sense molecules. Yet the same mutation appears also in the bone marrow stem cell and its progeny, like lymphocyte, and red blood cell, which do not become cancerous. Silencing the Philadelphia chromosome with anti-sense molecules will silence also its non cancerous kin, as well as  the patient.


Chromosomal translocations

Chromosomal translocations are also regarded as unfortunate mistakes which make the cell more aggressive. Like in Burkitt's lymphoma, which is supposed to be caused by two specific translocations. Recently one of them was found in healthy Dutch individuals (3): "The frequency of t(14;18) breakpoints in normal individuals is extremely high. At least half of all normal [Dutch] individuals harbor numerous B cells with a translocation." These startling observations lead to the following conclusions: chromosomal translocation is a physiological process which was hitherto detected only when amplified, e.g. in cancer. Sensitive PCR techniques reveal it in healthy cells as well. Since it is ubiquitous, it cannot be regarded as pre-malignant .

WOB controls cancer

Why not then regard cancer progression as a continuing WOB repair of an ongoing damage caused by carcinogens? Gene mutations are initiated by WOB to produce novel molecules, that correct  the carcinogenic damage.  Mutations and translocations are WOB solutions. True, as disease advances, they become more abundant, yet without them patient would have fared worse.


References

1.Stedman's Medical Dictionary. William & Wilkins WordPerfect software 1994.
2. Concise Medical Dictionary, Oxford University Press. Market House Books Ltd. 1998
3. Muller JR, Janz S, Goedett JJ, et al. Persistence of immunoglobulin heavy chain/C-MYC recombination-positive lymphocyte clones in the blood of human immunodefficiency virus-infected homosexual men. Proc.Natl Acad.Sci 92, 6577-6581, 1995.




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