[ RadSafe ] RE: LNT now NOT "reasonable"

Mon Mar 21 19:52:45 CET 2005

Friends,

Re NCRP-136, see:
http://cnts.wpi.edu/RSH/Docs/Correspondence/NCRP136/NCRP136Index.htm 

And our quick comments last Friday on the similar ICRP Committee 1 Task Group
Report:
http://cnts.wpi.edu/rsh/docs/Correspondence/ICRP-TG1comments.htm 

We anticipate that the LNT fraud will come apart in the assessment of the
ICRP Recommendations, perhaps including consideration of the extensive actual
science misconduct by authors committed to maintain the LNT and its profits.

Obviously, the LNT "debate" predates 1977. It was a major issue in the mid-
late-50s, and since. Before that in the late '40s from the medical/drugs
interest (suppressing data from the Manhattan Project research when the
medical/FDA etc. agency controls had been weakened.  But brought back strong
to constrain competition to medical/drug controls and profits.  This was
initiated by the drug companies and FDA in the mid- late-30s.

And "hormesis" bi-phasic response is, and has to be, the natural condition in
biology. Biological functions could not be maintained; life would not be
sustainable, otherwise. 

For example, two recent papers by Ed Calabrese that further document
voluminous current knowledge on the subject are:

1)  Invited paper:  Paradigm lost, paradigm found: the re-emergence of
hormesis as a fundamental dose response model in the toxicological sciences 

Edward J. Calabrese*

The quantitative features of the hormetic dose/response are described and
placed within the context of toxicology.

Abstract:  This paper provides an assessment of the toxicological basis of
the hormetic dose-response relationship including issues relating to its
reproducibility, frequency, and generalizability across biological models,
endpoints measured and chemical class/physical stressors and implications for
risk assessment. The quantitative features of the hormetic dose response are
described and placed within toxicological context that considers study
design, temporal assessment, mechanism, and experimental model/population
heterogeneity. Particular emphasis is placed on an historical evaluation of
why the field of toxicology rejected hormesis in favor of dose response
models such as the threshold model for assessing non-carcinogens and linear
no threshold (LNT) models for assessing carcinogens. The paper argues that
such decisions were principally based on complex historical factors that
emerged from the intense and protracted conflict between what is now called
traditional medicine and homeopathy and the overly dominating influence of
regulatory agencies on the toxicological intellectual agenda. Such regulatory
agency influence emphasized hazard/risk assessment goals such as the
derivation of no observed adverse effect levels (NOAELs) and the lowest
observed adverse effect levels (LOAELs) which were derived principally from
high dose studies using few doses, a feature which restricted perceptions and
distorted judgments of several generations of toxicologists concerning the
nature of the dose-response continuum. Such historical and technical blind
spots lead the field of toxicology to not only reject an established
dose-response model (hormesis), but also the model that was more common and
fundamental than those that the field accepted.  c 2005 Elsevier Ltd. All
rights reserved.

Keywords: Hormesis; U-shaped; J-shaped; Homeopathy; Dose-response; Biphasic;
Risk assessment; Threshold; Linearity; History of science; History of
medicine; Toxicology

2) Critical Reviews in Toxicology, 35:89-295, 2005  [NOTE: 207 PAGES!  PDF IS
2.5 MB]

Hormetic Dose-Response Relationships in Immunology: Occurrence, Quantitative
Features of the Dose Response, Mechanistic Foundations, and Clinical
Implications

Edward J. Calabrese

Environmental Health and Health Sciences, University of Massachusetts,
Amherst, Massachusetts, USA

This article provides an assessment of the occurrence of
immune-system-related hormetic-like biphasic dose-response relationships.
Such dose-response relationships are extensive, with over 90 different immune
response-related endpoints reported, induced by over 70 endogenous agonists,
over 100 drugs, and over 40 environmental contaminants. Such hormetic
responses were reported in over 30 animal models, over a dozen mammalian and
human cell lines. These findings demonstrate that immune-system-related
hormetic-like biphasic dose-response relationships are common and highly
generalizable according to model, endpoint, and chemical class. The
quantitative features of the dose response are generally consistent with
previously published examples of hormetic dose responses for other biological
endpoints. These findings were generally recognized and explicitly discussed
by the original authors, often with consideration given to possible
mechanistic foundations as well as numerous clinical implications. Despite
the recognition by individual authors of the hormetic nature of these
observed responses, the overall widespread nature of immune-related hormetic
responses has been only little appreciated, with a general lack of insight
into the highly generalizable nature of this phenomenon as well as the
complex regulatory networks affecting biological switching mechanisms that
result in the hormetic responses.

Keywords Hormesis, U-Shaped, J-Shaped, Immune Stimulation, Lymphocyte
Stimulation, Metals, Stimulatory, Inhibitory, Opioids, Cytokines,
Interleukins, Dose Response

Let me know if you want either of these papers for review.

Regards, Jim Muckerheide

________________________________

From: John Jacobus [mailto:crispy_bird at yahoo.com]
Sent: Sun 3/20/2005 12:26 PM
To: howard long; Syd H. Levine; Gerald Nicholls; radsafe at radlab.nl;
rad-sci-1 at WPI.EDU; Muckerheide, James
Subject: Re: LNT now NOT "reasonable"

I always offer to provide others information to make
up their own minds.  I would suggest that if you do go
the the Radiation Safety and Health Web site you read
the information critically.  I would also suggest that
people, including Howard, read the NCRP Report 136 to
understand the underpinnings of the LNT.
http://www.ncrponline.org/rpt136.html  I do not know
how one can make an intelligent decision without
understanding all of the facts. 

Despite what Howard says the LNT is reasonable, not
perfect.  It is a hypothesis.  Research being
undertaken by DOE may further expand our understanding
of such phenomenons as the bystander effect.
http://lowdose.tricity.wsu.edu/
Such work may even provide evidence that hormesis is
not what its proponents suggest. As the McGregor and
Land report of 1977 shows, low does of radiation do
increase cancer.  I believe that this report was
published before there was any LNT/hormesis
controversy.  Therefore, its result are not biased to
support the LNT, even if Howard says it is. 

By the way, I must thank Howard Long for leading to
the paper. Again, if anyone wants a copy, let me know.

--- howard long <hflong at pacbell.net> wrote:

> John has kindly corrected my address for rad-sci, at
> which there IS ample data that LNT and ALARA are now
> NOT "reasonable":
> http://cnts.wpi.edu/RSH/Docs/index.html
>
>
> Howard Long
>
> John Jacobus <crispy_bird at yahoo.com> wrote:
> I will conceed that the LNT is a hypothesis that
> attempts to fit known data to some mathematic model.
>
> Does it work in all cases? Within the limits of the
> data, it is probably reasonable.
>
> As for the number of cases that support hormesis,
> what
> do you mean? Actual data like the McGregor and Land
> study of 1977 that shows no hormetic effect?
> Ancedotal stories or cherry picking of data? Bits
> and
> pieces of data from other work, like taking one line
> of from the McGregor and Land paper of 1979, does
> not
> really constitute a study. Consider my arguement
> that
> the McGregor and Land article of 1979 showed a
> difference between observed cancers and expected
> based
> on the LNT. Again, the LNT provides an a
> mathematical
> estimate based on large populations. After all
> cancer
> is a stochastic event, of estimates of cancer based
> on
> any model will be estimates. One of the things I
> like
> to see are error bars of levels of confidence in the
> data. They often speak volumes about the work.
>
> The statement that the estimated risk as an absolute
> shows a lack of understanding of basic science and
> epidemiology. Howard Long claims to have studied
> epidemiology, but does bring any of that knowledge
> to
> the argument. Rather, there is this blind faith in
> what others say. I certainly do not have any divine
> insight, but I am willing to look at the data and
> the
> agruments for and against. I would expect that
> others
> would try to make a similar effort, but I am
> probably
> deluding myself. However, I am willing to give
> others
> what I have so they can ponder the information. I do
> not dislike Dr. Long, just his inability to
> understand
> what he cites. Maybe he is the one who has blind
> faith.
>
> I am please to hear that you are puzzled. Maybe it
> will lead to looking at the data and asking
> questions.
> Again, if you would like copies of any of the papers
> I mention, let me know.
>
> --- "Syd H. Levine" wrote:
>
> > John:
> >
> > Would you concede that there is sufficient
> evidence
> > to question the validity
> > of LNT given the number of studies that seem to
> > support hormesis (even if
> > the science is not sterling)? Or do you simply
> > believe LNT is clearly
> > correct based on some insight I seem to lack? I am
> > puzzled by your take on
> > this matter and what seems to be a certain
> > stubbornness (and dislike for Dr.
> > Long).
> >
> > Syd H. Levine
> > AnaLog Services, Inc.
> > Phone: 270-276-5671
> > Telefax: 270-276-5588
> > E-mail: analog at logwell.com
> > URL: www.logwell.com
> >
> > ----- Original Message -----
> > From: "John Jacobus"
> > To: "howard long" ; "Gerald
> > Nicholls"
> > ;
> > ;
> > Sent: Friday, March 18, 2005 6:44 PM
> > Subject: Re: [ RadSafe ] Do better than John
> Snow's
> > Work. Medical Ethics?
> >
> >
> > >I guess the thing that has always bothered me is
> > that
> > > there is no control matching between the general
> > > population and the irradiated apartment
> dwellers.
> > > Even in this country you see differences in
> cancer
> > > distributions between more and less densely
> > populated
> > > areas, age, sex, etc. Is it possible most
> > apartment
> > > dwellers are under 50, which would bias the
> data?
> > >
> > > The numbers seem fast and loose. Of course,
> being
> > > skeptical is not permitted. You must accept
> > whatever
> > > is fed to you.
> > >
> > > --- howard long wrote:
> > >> Thank you for this serious response to my
> tongue
> > in
> > >> cheek proposal.
> > >> It deserves a better answer than I can give, so
> I
> > am
> > >> including the rad-sci list in hopes that
> someone
> > >> like Muckerheide will point out the
> retrospective
> > >> studies already done.
> > >>
> > >> I do fear that lawsuit for imaginary damage is
> > the
> > >> main obstacle to a properly controlled study.
> > >>
> > >> Howard Long
> > >>
> > >> Gerald Nicholls
> > >> wrote:
> > >> Howard Long wrote:
> > >>
> > >> "The Taiwan "Study" (J Am Phys & Surg 9:1,
> > pp6-11)
> > >> is at least as
> > >> impressive as was John Snow's observation of
> more
> > >> disease on one side of
> > >> a London street than the other having a
> different
> > >> water supply.This at
> > >> least calls for a test, "taking off the pump
> > >> handle", exposing another
> > >> population to 0.4 Sv over 10 years, to
> reproduce
> > >> very low cancer and
> > >> fetal abnormality rates..
> > >>
> > >> Are ambulance chasers like the TV lawyers
> > soliciting
> > >> anyone with or
> > >> without trouble who ever was near a brake
> lining
> > >> (asbestos), had heart
> > >> trouble (aspirin family), etc, ready to block
> > this
> > >> science?"
> > >>
> > >> It seems to me that Snow's work on the spread
> of
> > >> cholera in 19th
> > >> century London is far more scientifically
> > impressive
> > >> than the Taiwan
> > >> study. Snow proposed that cholera was
> transmitted
> > by
> > >> contaminated water
> > >> in 1849 (in conflict with the generally then
> held
> > >> idea of inhalation of
> > >> vapors) and was able to prove his theory in
> 1854
> > >> during a particularly
> > >> tragic outbreak of the disease. The authors of
> > the
> > >> Taiwan study have
> > >> documented their observations and pointed out
> the
> > >> need for further
> > >> study, but not proved their case. One of
> > >> recommendations is to design
> > >> future experiments so that hormetic effects can
> > be
> > >> studied.
> > >>
>
=== message truncated ===

+++++++++++++++++++
"A positive attitude may not solve all your problems, but it will annoy
enough people to make it worth the effort." Herm Albright

-- John
John Jacobus, MS
Certified Health Physicist
e-mail:  crispy_bird at yahoo.com

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