RE: Paul Unschuld's unanswerable question - HORMESIS

[Guest guest]

Science is a template for acquiring certainty in knowledge. From the

Empiricist tradition; Popper; and Kuhn and the expression of this in the

mathematical statistics notion of P values to determine the 'Absence of

Verification of the Null Hypothesis' (rather than a 'Proof of the

Hypothesis' itself which is impossible) .. we acquire a methodology that

gives us this certainty that no other methodology in the history of

civilisation has done. Let's not forget that when we knock western Science.

On the other hand this Science is as Emmanual observed a template for the

pedantic and unimaginative, which I see has spawned a ponderous monolith we

know as 'the research industry'.

 

Despite the shortcomings there is still room for originality, creativity and

intuition in Science. I think a good example is found in development of the

notion of hormesis in toxicology. Somehow these ideas are squeezing into the

rigid template, opining it up and making it possible to 'do science' in a

TCM context, AND to have an eye for the criteria Jim points out.

 

Sammy.

 

 

Hormesis is a non-linear biological response to a substance. " low-dose

stimulation and a high-dose inhibition " [1].

 

Calabrese, admits the phenomenon has been marginalised in the west because

of the inability to fit it into the current scientific paradigm, regardless

of its empirical reality[2].

 

From my own area of interest: I regarded the biphasic response of prostate

cells to androgens as a specialised adaptation;

now it appears that hormesis is a general phenomenon which may eventually

acquire conventional clinical acceptance[3].

 

The rationale for treating prostate cancer in TCM as a disease of deficiency

rather than one of excess grows, despite the increasing practice of

'castration therapy' in China for the problem, and the continued popularity

of 'TCM-like' PC-SPES analogs in the west. That each views the others

medicine in a framework of parody is hopefully a temporary disorder:

incoherence1 (not incoherence2).

 

 

Refs: http://www.ncbi.nlm.nih.gov/entrez/

 

1: Toxicol Sci. 2003 Feb;71(2):246-50. Related Articles, Links

 

 

Comment on:

Toxicol Sci. 2003 Feb;71(2):134-6.

 

The hormetic dose-response model is more common than the threshold model in

toxicology.

 

Calabrese EJ, Baldwin LA.

 

Department of Environmental Health Sciences, University of Massachusetts,

Amherst, Massachusetts 01003, USA. edwardc

 

The threshold dose-response model is widely viewed as the most dominant

model in toxicology. The present study was designed to test the validity of

the threshold model by assessing the responses of doses below the

toxicological NOAEL (no observed adverse effect level) in relationship to

the control response (i.e., unexposed group). Nearly 1,800 doses below the

NOAEL, from 664 dose-response relationships derived from a previously

published database that satisfied a priori entry criteria, were evaluated.

While the threshold model predicts a 1:1 ratio of responses " greater than "

to " less than " the control response (i.e., a random distribution), a 2.5:1

ratio (i.e., 1171:464) was observed, reflecting 31% more responses above the

control value than expected (p < 0.0001). The mean response (calculated as %

control response) of doses below the NOAEL was 115.0% +/- 1.5 standard error

of the mean (SEM). These findings challenge the long-standing belief in the

primacy of the threshold model in toxicology (and other areas of biology

involving dose-response relationships) and provide strong support for the

hormetic-like biphasic dose-response model characterized by a low-dose

stimulation and a high-dose inhibition. These findings may affect numerous

aspects of toxicological and biological/biomedical research related to

dose-response relationships, including study design, risk assessment, as

well as chemotherapeutic strategies.

 

PMID: 12563110 [PubMed - indexed for MEDLINE]

 

 

 

2. Hum Exp Toxicol. 2000 Jan;19(1):32-40.

 

 

The marginalization of hormesis.

 

Calabrese EJ, Baldwin LA.

 

Department of Environmental Health Sciences, School of Public Health,

University of Massachusetts, Amherst, MA 01003, USA.

 

Despite the substantial development and publication of highly reproducible

toxicological data, the concept of hormetic dose-response relationships was

never integrated into the mainstream of toxicological thought. Review of the

historical foundations of the interpretation of the bioassay and assessment

of competitive theories of dose-response relationships lead to the

conclusion that multiple factors contributed to the marginalization of

hormesis during the middle and subsequent decades of the 20th century. These

factors include: (a) the close-association of hormesis with homeopathy lead

to the hostility of modern medicine toward homeopathy thereby creating a

guilt by association framework, and the carry-over influence of that

hostility in the judgements of medically-based pharmacologists/

toxicologists toward hormesis; (b) the emphasis of high dose effects linked

with a lack of appreciation of the significance of the implications of low

dose stimulatory effects; © the lack of an evolutionary-based mechanism(s)

to account for hormetic effects; and (d) the lack of appropriate scientific

advocates to counter aggressive and intellectually powerful critics of the

hormetic perspective.

 

Publication Types:

Review

Review, Tutorial

 

PMID: 10745293 [PubMed - indexed for MEDLINE]

 

 

3. Crit Rev Toxicol. 2003;33(3-4):305-53. Related Articles, Links

 

Chemotherapeutics and hormesis.

 

Calabrese EJ, Baldwin LA.

 

Department of Environmental Health Sciences, Morrill Science Center,

University of Massachusetts, Amherst, MA 01003, USA.

edwardc

 

This article represents the first comprehensive assessment of hormetic

effects of chemotherapeutic agents. Hormetic dose-response relationships

were reported for a wide range of chemotherapeutics, including antibiotics,

antiviral, and antitumor agents as well as substances that affect hair

growth, prostate function, cognitive performance, and numerous other

endpoints. Particular attention was given to assessing the quantitative

features of the dose response, the underlying mechanistic features of the

biphasic nature of the dose response, and the clinical implications of

hormetic responses. Recognition of the hormetic-like biphasic nature of the

dose response is expected to have an important impact on the design of

experiments to assess chemotherapeutics and how such agents may be employed

more successfully in clinical applications.

 

Publication Types:

Review

Review, Tutorial

 

PMID: 12809428 [PubMed - indexed for MEDLINE]