Roger Masters, Ph.D.

Presentation + Questions & Answers
For ADD-Holistic Discussion Group
http://www.HolisticMed.Com/add/


To: add-holistic@mLists.net
From: mgold@tiac.net
Subject: ADD Introduction of Visiting Expert!
Date: Sun, 14 Nov 1999 14:37:39 -0700 (MST)

Hi!

I am very pleased to introduce our Visiting Expert, Roger D. Masters, Ph.D. Dr. Masters is Nelson D. Rockefeller Professor Emeritus in the Dartmouth College Department of Government. He heads the Dartmouth Foundation for Neuroscience and Society. For several decades he has researched the causes of violence and other dysfunctional human behavior such as ADD, ADHD, drug abuse and the like. His viewpoint, which has been published widely, is that toxins in the environment have subtle effects on brain and neural functions which are ultimately manifested in behaviors which many social scientists and politicians prefer to attribute to social dynamics.

Dr. Masters presented a groundbreaking study related to lead and silicofluorides at the recent 17th International Neurotoxicology Conference ( "Children's Health and the Environment," Little Rock, Arkansas, October 17-20, 1999). I feel fortunate that Dr. Masters has agreed to take some time to help us better understand the behavioral effects of lead and other toxins. Please join me in welcoming Dr. Masters to our online discussion group! [Clap, clap, clap, clap!]

Dr. Masters' opening email will be sent out tomorrow (Monday).

Below are a few relevent excerpts from his Curriculum Vitae:

Education:


Behavioral Research (1995-1998)


Awards:


Work in progress: Analysis of neurotoxicity associated with pollution, poor diet, and lifestyle as risk factors in vi` crime, health, and social behavior.

Publications:

Editor and co-translator, Rousseau's First and Second Discourses (New York: St. Martin's, 1964)
The Nation is Burdened: American Foreign Policy in a Changing World (New York: Knopf, 1967)
The Political Philosophy of Rousseau (Princeton: Princeton University Press, 1968)
Editor, Rousseau's Social Contract, with Geneva Manuscript and Political Economy (New York: St. Martin's Press, 1978)
Co-Editor with Margaret Gruter, Ostracism: a Biological and Social Phenomenon (New York: Elsevier Science Publishers, 1986)
The Nature of Politics (New Haven: Yale University Press, 1989)
Co-Editor with Christopher Kelly, Rousseau, Judge of Jean-Jacques; Collected Writings of Rousseau, Vol. 1 (Hanover, NH: University Press of New England, 1990).
Co-Editor with Glendon Schubert, Primate Politics (Carbondale, IL: Southern Illinois University Press, 1991); paperback, with new Preface (University Press of America, 1994).
Co-Editor with Margaret Gruter, The Sense of Justice: Biological Foundations of Law (Newbury Park, CA: Sage, 1992)
Co-Editor with Christopher Kelly, Rousseau's First Discourse and Polemics; Collected Writings of Rousseau, Vol. 2 (Hanover, NH: University Press of New England, 1992).
Co-Editor with Christopher Kelly, Rousseau's Second Discourse. Polemics, and Political Economy; Collected Writings of Rousseau, Vol. 3 (Hanover, NH: University Press of New England, 1993)
Beyond Relativism: Science and Human Values (Hanover, NH: University Press of New England, 1993)
Co-Editor, with Michael T. McGuire, The Neurotransmitter Revolution (Carbondale, IL: Southern Illinois University Press, 1994)
General Editor, Gruter Institute Reader: Biology, Law, and Human Behavior (Computerized Database for Customized Books of Readings; New York: McGraw Hill [Primis])
Co-Editor with Christopher Kelly, Rousseau's Socal Contract, Essay on the Virtue of Heroes, Geneva Manuscript; Collected Writings of Rousseau, Vol. 4 (Hanover, NH: University Press of New England, 1994)
Co-Editor with Christopher Kelly, Rousseau's Confessions, Collected Writings of Rousseau, Vol. 5 (Hanover, NH: University Press of New England, 1996)
Machiavelli, Leonardo, and the Science of Power (University of Notre Dame Press. 1996)
Fortune is a River: Leonardo da Vinci and Niccole Machiavelli's Magnificent Dream to Change the Course of Florentine History (New York: Free Press, 1998). Paperback edition, New York: Plume, 1999).

Over 150 scholarly articles and journalistic essays in English, French, and German, including contributions to Quarterly Review of Biology, Ethology and Sociobiology, American Political Science Review, World Politics, Politics and Life Sciences, Environmental Toxicology, International Journal of Environmental Studies, etc.



Neuroscience, Toxic Chemicals and ADD/ADHD

Roger D. Masters

Dartmouth College

Most current discussions of ADD/ADHD have paid insufficient attention to recent work in cognitive neuroscience. The education establishment, the medical community, and the public at large often seem to believe that each of these conditions is a single category for which drug therapy (e.g., with ritalin) is the normal response. I believe this is superficial and, indeed, dangerous for two reasons. First, among the many sources of the behaviors associated with ADD and ADHD are the exposure to and uptake of lead and other heavy metals that are toxic to brain cells. Realization of this evidence has clear implications for treatment. Second, the biological or psychological effects of a prolonged course of drug therapy with ritalin or other comparable treatments are, to my knowledge, unknown. Although numerous specialists have privately agreed with this concern, it is rarely emphasized in the press that the nearly ubiquitous reliance on drug treatment without long-term testing may be risky for some if not most children.

These points are related, since there is an alternative approach to the portion of the ADD/ADHD population whose symptoms are the result of heavy metal neurotoxicity.

First, the issue of etiology. There is little question that the frequency of ADD/ADHD has greatly increased in recent years (though some still pretend it is simply more visible than in the past). I saw one report from Milwaukee that suggested as much as a doubling in ADD/ADHD cases over the last decade. Such large increases usually do not come from increased visibility of a genetic condition that influences a fixed percentage of children.

One factor that can explain this is heavy metal absorption in the brain (Minder, et al., 1994; Needleman, 1999). Although not all studies confirm the association (e.g., Kahn, Kelly, and Walker, 1995), Tuthill (1996) also found that a large proportion of ADHD children in one Massachusetts community had absorbed high levels of lead. Others have suggested similar effects of manganese toxicity. In animal studies, moreover, impulsive responses are significantly increased by lead exposure (Brockel and Cory-Slechta, 1997).

Mechanisms that can explain this associated are also known. Lead is known to downregulate several neurotransmitters, including dopamine and glutamate; manganese downregulates serotonin (Bryce-Smith, 1983; Needleman, 1991, 1996). In addition, these heavy metals have effects related to the crucial role of calcium, which functions as a neurotransmitter and co-factor in many brain systems.

Uptake of heavy metals from the environment is increased by dietary deficits in calcium, which is a divalent cation -- that is, an element with a positive ionic chage of 2. Heavy metals like lead, cadmium, and manganese are also divalent cations, so they can occupy sites on or in neurons normally occupied by calcium. Hence heavy metal neurotoxicity both downregulates essential neurotransmitters, including those required for impulse control, and reduces the normal effect of calcium (Aschner & Kimelberg, 1996; Masters, Hone and Doshi, 1998).

It takes only a brief look at a textbook in cognitive neuroscience to see how important these effects can be. For example, the inhibitory function of the basal ganglia relies in part on dopamine, which is downregulated by lead (e.g., Gazzaniga, et al., 1998: pp. 413-420). And calcium plays a key role in the hippocampus, essential to the basic learning process known as "Long Term Potentiation" or LTP (Gazzaniga, et al., 1998: pp. 283-288). Not surprisingly, ADHD has been linked to deficits in dopamine function (Cook, et al., 1995).

Hence there are plausible explanations for the observation that heavy metals could account for a substantial portion of ADD/ADHD cases, especially since early lead exposure is so widespread and damaging to children (Aschengau, et al, 1993; Bellinger, et al., 1994; Mielke, 1998; Levitt, 1999). In one early study by Chisholm, although said to be flawed by many neuroscientists, chelation improved the symptoms of a small number of ADHD children with high lead levels. More work is badly needed in this area, since lead chelation might replace drug treatment for a subset of ADD/ADHD cases.

Another major approach, focusing on prevention, is suggested by research that I have been conducting with Myron Coplan. We have found that lead levels in children are significantly increased by exposure to water treated with either fluosilicic acid or sodium silicofluoride. These "silicofluorides" (which are used for over 94% of the water fluoridation in the U.S.) have never been fully tested, though early studies in the 1930's showed substantial differences in metabolism between sodium silicofluoride and sodium fluoride (the chemical used in tests of fluoridation safety by supporters and critics alike, even though it is employed in only about 6% of American water fluoridation).

In general, silicofluorides enhance the uptake of lead from old houses or public water supplies, particularly among the poor and minorities whose diets are insufficient in calcium and other essential minerals.

Reanalyzing a Massachusetts survey of lead levels in 280,000 children (Bailey et al., 1994), we found significantly higher lead levels in SiF treated communities, controlling for other risk factors for lead toxicity (Masters and Coplan, 1999). This finding has now been confirmed using the national sample in NHANES III as well as in a sample of over 120,000 children from New York towns of 15,000 to 75,000 population (Masters, Coplan, and Hone, 1999).

By reanalyzing a NIJ sample of urinalysis of over 30,000 criminals in 24 cities, we have also found higher rates of alcoholism, substance abuse and crime to be associated with SiF usage (Masters and Coplan, in press). Indeed, in the communities covered by our other studies, we also see more crime and alcoholism associated with SiF usage. Since Manuzza (1989, 1998) and others have indicated that there is a correlation between hyperactivity and criminal behavior, these associations are probably linked elements of a pattern of weakened impulse control.

We are actively seeking information on ADD/ADHD rates, and would appreciate any reliable geographic data that would allow us to compare numbers of children receiving drug treatment and/or special education services in communities using different approaches to water treatment. (For a sample of 16 towns in New York, we found that the percent of enrolled high school students reported by the school nurse to take medication for ADD/ADHD is 38% higher where SiF is in use, as compared to non-fluoridating communities of similar size).

We would welcome collaboration with any researchers who have relevant data. It may well be, for example, that OTHER environmental factors are associated with higher rates of ADD/ADHD. Given the importance of the issue, it is rather astonishing that so little geographic data has been collected. And since neurotoxicity is probably one of the etiological pathways (along with early developmental insults of other sorts and probably genetics), such ecological data would be especially valuable.

NOTE: For copies of our publications, please send an e-mail request with your address to: Suzanne.Saxton@Dartmouth.edu


BIBLIOGRAPHY

Aschengau, A., Ziegler, S., and Cohen. 1993. "A. Quality of Community Drinking Water and the Occurrence of Late Adverse Pregnancy Outcomes," Archives of Environmental Health 48: 105-113.

Aschner, M. and Kimelberg, M. 1996. The Role of Glia in Neurotoxicity. Boca Raton,FL, CRC Press.

Bailey, A.J., Sargent, J.D., Goodman, D.C., Freeman, J., and Brown, M.J. 1994. Poisoned Landscapes: The Epidemiology of Environmental Lead Exposure in Massachusetts Children 1990-1991. Social Science Medicine 39: 757-776.

Bellinger D et al, "Pre-and Postnatal Lead Exposure and Behavior Problems in School-Aged Children", Environmental Research, v 66 (1), p 12-30, (July 1994)

Brockel, Becky A., Cory-Slechta, Deborah A. "Lead, Attention, and Impulsive Behavior: Changes in a Fixed-Ratio Waiting-for-Reward Paradigm", Pharmacology Biochemistry and Behavior , June 1998,Vol.60, No. 2: 545-552.

Bryce-Smith, D. 1986. " Environmental Chemical Influences on Behaviour and Mentation," Chemical Sciety Review, 15, 93-123.

Cook, E. H Jr.,et al. 1995. "Association of Attention Deficit disorder and the dopamine Transporter gene. "American Journal of Human Genetics,56,

Gazzaniga, Michael, Ivry, Richard B. and Mangun, George R. 1998. Cognitive Neuroscience. New York: W. W. Norton.

Kahn, CA., Kelly, PC., Walker, WO. 1995. "Lead screening in children with attention deficit hyperactivity disorder and developmental delay", Clinical Pediatrics,, Sept 1995, Vol 34, No. 9: 498-501.

Minder, Barbara, Das-Smaal, Edith A., Brand, Eddy F. J. M., Orlebeke, Jacob F. 1994. "Exposure to Lead and Specific Attentional Problems in Schoolchildren", Journal of Learning Disabilities , June/July 1994, Vol. 27, no. 6: 393-398.

Levitt, Miriam. 1999. "Toxic Metals, Preconception, and Early Childhood Development," Social Science Information, 38: 179-201.

Manuzza, S., et al. 1989. "Hyperactive Boys Almost Grown Up," Archives of General Psychiatry, 46: 1073-1079.

Manuzza, S., et al., 1998. "Adult Psychiatric Status of Hyperactive Boys Grown Up," American Journal Of Psychiatry 155: 493-498.

Masters, Roger D. and Coplan, Myron. J. 1999a. "Water Treatment with Silicofluorides and Lead Toxicity," International Journal of Environmental Studies, 56: 435-449.

Masters, Roger D. and Coplan, Myron J. 1999b. "A Dynamic, Multifactorial Model of Alcohol, Drug Abuse, and Crime: Linking Neuroscience and Behavior to Toxicology," Social Science Information. In press.

Masters, Roger D., Coplan, Myron J. and Hone, Brian T. 1999a. "Silicofluoride Usage, Tooth Decay, and Children s Blood Lead," Poster Presentation, Environmantal Influences on Children: Brain, Development, and Behavior, Conference at New York Academy of Medicine, New York, NY, May 24-25, 1999.

Masters, Roger D., Coplan, Myron J. and Hone, Brian T. 1999b. "Heavy Metal Toxicity, Development, and Behavior," Poster Presentation, 17th International Neurotoxicology Conference, Doubletree Hotel, Little Rock, ARK., October 17-20, 1999.

Masters, Roger D., Hone, Brian T., and Doshi, Anil. 1998. "Environmental Pollution, Neurotoxicity, and Criminal Violence," in J. Rose., ed., Environmental Toxicology (London: Gordon and Breach), pp. 13-48.

Mendelsohn, Alan L.; Dreyer, Benard P.; Fierman, Arthur H.; Rosen, Carolyn M.; Legano, Lori A.; Kruger, Hillary A.; Limß, Sylvia W. and Courtlandt, Cheryl D. 1998. "Low-Level Lead Exposure and Behavior in Early Childhood" Pediatrics, Vol. 101 No. 3 March 1998, p. e10.

Mielke, H. 1998. "Lead in the Inner Cities," American Scientist, 87:62-73.

Needleman, Herbert L., ed. 1991. Human Lead Exposure. Boca Raton, FL: CRC Press.

Needleman, Herbert L., et al., 1996. "Bone Lead Levels and Delinquent Behavior, JAMA 275: 363-69.

Needleman, Herbert L. 1999. "Environmental Neurotoxins and Attention Deficit Disorder," Presentation at Conference on Environmental Neurotoxins and Developmental Disability, N. Y. Academy of Medicine, New York (May 24-25, 1999).

Tuthill, R. W. 1996. "Head Lead Levels Related to Children s Classrooom Attention-Deficit Behavior," Archives of Environmental Health, 51: 214-20.



To: add-holistic@mLists.net
From: "Dr. Gary Erkfritz"
Subject: Re: ADD Introduction of Visiting Expert!
Date: Sun, 14 Nov 1999 14:16:52 -0800

Dr. Masters, the first thing I'd like to know if how and why you made from government to toxicology? That must be an interesting story.
Gary



To: add-holistic@mLists.net
From: Roger.D.Masters@Dartmouth.EDU
Subject: Re: ADD Introduction of Visiting Expert!
Date: Mon, 15 Nov 1999 22:29:32 -0700 (MST)

>To: add-holistic@mLists.net
>From: "Dr. Gary Erkfritz"
>Subject: Re: ADD Introduction of Visiting Expert!
>Dr. Masters, the first thing I'd like to know if how and why you made
>from government to toxicology? That must be an interesting story.

I was trained as a political philosopher (studying with Leo Strauss at Chicago), and working primarily on Rousseau. In 1968 I decided to look at modern biology and evolutionary theory (because Rousseau claimed that humans descended from -- or were originally -- primates like gorillas or chimpanzees). One thing led to another and I spent years on the biology of behavior (focusing on experimental studies of the nonverbal displays of presidential candidates and their effects on voters). IN 1989, published THE NATURE OF POLITICS (with both this empirical work and theoretical discussion). See also BEYOND RELATIVISM and MACHIAVELLI, LEONARDO & THE SCIENCE OF POWER). I then did a good deal of work with lawyers on biology and law, which led to a request from the Commissioner of Corrections of Vermont (where I live) that I study brain chemistry and crime. Since I'd done a book with Michael McGuire on serotonin and social behavior (including low 5HT and aggressive behavior), I agreed. That led to a meeting where I met an independent researcher who was studying manganese toxicity and crime. I originally thought the idea nonsense, set out to disprove it with EPA Toxic Release data, and confirmed it! I also began to study lead, and that resulting in the question from Myron Coplan if I had ever studied fluoride as a toxin. One thing led to another, including several grants, and now I'm over my head!

roger masters



To:
From: "Dale Goudey"
Subject: Re: ADD Introduction of Visiting Expert!

Date: Tue, 16 Nov 1999 10:23:00 -0800

Dr. Rodger Masters,

>One thing led to another, including several grants, and now I'm over my
>head!

If you ever start to see daylight, please consider looking into the toxic plight of kids with autism. There are SPEC scans of children with autism which imply that autism is the same thing as ADD/ADHD, only worse. See this site. www.nids.net Many of the kids have a damaged sulfur detoxification pathway. One toxin that can cause this is mercury, which crosses the placenta. Some of the children are being chelated to remove this toxin.

Polly



To: add-holistic@mLists.net
From: Roger.D.Masters@Dartmouth.EDU (Roger D. Masters)
Subject: Re: ADD Introduction of Visiting Expert!

Date: 16 Nov 1999 14:47:24 EST

I would be very happy to work WITH you (or anyone else) on the environmental factors associated with Autism. I've been trying for some time to locate geographic data on rates of incidence. If you know of any sources, they would be invaluable.

I've been conscious of possible neurochemical links to autism ever since a dermatologist explained that rubbing the skin releases nitric oxide (which functions as a muscle relaxant). I had the hunch at the time (based on hearing an interview with Temple Grandin) that this mechanism might explain the use of pressure on the skin which she (and others) have found to be effective.

If there are neurochemical dysfunctions involved, then of course neurotoxicity is a possible candidate for etiology. In many cases, of course, more than one neurotoxin (alone or in synergistic interaction) is often responsible for the symptoms. This makes the analysis VERY difficult, but if one starts out expecting complexity, it is easier to find.

If anyone knows a source of funding for this research, I am President of a small foundation (as yet, we have no money, only dreams) that can serve as the basis for grants. I'm also happy to recruit Dartmouth undergraduates to help with the research (they can be extremely good). My principal problem is the limitation of my own time. However, since I have a colleague with an autistic child, I have a personal incentive to help.

roger masters



To: add-holistic@mLists.net
From: "John V DOMmisse, MD"
Subject: Re: ADD Introduction of Visiting Expert!

Date: Mon, 15 Nov 1999 23:10:46 -0700

Roger.D.Masters@Dartmouth.EDU wrote:
> .... > meeting where I met an independent researcher who was studying
> manganese toxicity and crime. I originally thought the idea nonsense,
> set out to disprove it with EPA Toxic Release data, and confirmed it! I
> also began to study lead, and that resulting in the question from Myron
> Coplan if I had ever studied fluoride as a toxin. One thing led to
> another, including several grants, and now I'm over my head!

Dr Masters,
Have you come across Steven Schoenthaler's work on nutrient deficiencies and juvenile delinquency, violent behavior, etc.? I believe he is still at the U of Ca at Stanislaus, a PhD in psychology who has ventured into nutrient biochemistry and behavior.

John Dommisse MD

Nutritional & Metabolic (Tele)Medicine
http://www.galaxymall.com/health/Nutrnl_Mtblc
Tucson,AZ,USA 85718-5892 Fax 520-577-1743 Ph.-1940



To: add-holistic@mLists.net
From: Roger.D.Masters@Dartmouth.EDU (Roger D. Masters)
Subject: Re: ADD Introduction of Visiting Expert!

Date: 16 Nov 1999 14:49:27 EST

Yes. Schoenthaler's work was among the first that I noted (see the chapter with Hone and Doshi in J. Rose, ed., ENVIRONMENTAL TOXICOLOGY, Gordon & Breach, 1998). More generally, this type of research - esp. with the use of head hair analysis for a broad spectrum of toxins -- is extremely useful as a means of monitoring toxic uptake.

roger masters



To: add-holistic@mLists.net
From: "John V DOMmisse, MD"
Subject: Re: ADD: Neuroscience, Toxic Chemicals and ADD/ADHD

Date: Mon, 15 Nov 1999 22:51:15 -0700

Prof. Masters,
I applaud your reference-based exposition of this subject. I attempted the same approach in a paper that is published only on my website (I haven't had the time to submit it anywhere); if you have the time, I'd appreciate your taking a quick look at it and letting me know what you think of it. I don't recall but hope that at least one of my references is to your work!

John Dommisse

John V DOMmisse MBChB(CapeTown), FRCP(Canada)
Nutritional & Metabolic (Tele)Medicine
http://www.galaxymall.com/health/Nutrnl_Mtblc
http://Thyroid.about.com/library/weekly/aa092299.htm
1840 E River Rd, Ste 210
Tucson,AZ,USA 85718-5892 Fax 520-577-1743 Ph.-1940



To: add-holistic@mLists.net
From: Roger.D.Masters@Dartmouth.EDU (Roger D. Masters)
Subject: Re: ADD: Neuroscience, Toxic Chemicals and ADD/ADHD

Date: 16 Nov 1999 14:52:44 EST

I would be very happy to look at your paper.

roger masters



To: add-holistic@mLists.net
From: mgold@tiac.net
Subject: Questions for Visiting Expert

Dr. Masters,

I have several questions. Your thoughts would be helpful to me and I believe would interest list members as well.

  1. If I remember correctly, some of the the earlier studies related to lead and behavioral effects were criticized because socioeconomic factors were not factored into the calculations. In other words, some people said that ADD/ADHD was more common in families with lower socioeconomic status. Higher lead exposure was also more common in families with lower socioeconomic status. Therefore the lead-ADD connection might just be a coincidence.

    It is my understanding that Tuthill, R.W. put this criticism to rest by controlling for socioeconomic factors, thereby showing a connection between lead exposure and ADD.

    Is this your understanding of the issue? Are there any other recent studies that controlled for socioeconomic status?

  2. I have heard that some common sources for lead exposure include lead in soil dust, lead paint dust (including exterior paint), pollution from factories, lead dust on hands during food preparation, ????.

    Are there any steps that families can take to reduce their likely exposure to lead? We have many parents on our discussion group and any practical steps or ideas to consider would be extremely useful.

  3. Are there any steps that families can take to reduce their changes of overexposure to manganese?

  4. There are some people who might consider EDTA chelation for lead. I am aware a study led by Dr. Boyd Haley of the Univ. of Kentucky showing potential adverse effects on the brain from EDTA chelation with concurrent exposure to mercury (Hg) from food, mercury amalgam fillings, endogenous Hg, etc. I have heard from a third party that Dr. Haley suggests avoiding EDTA chelation until mercury urine measurements are below a certain level. (I haven't spoken with Dr. Haley myself.)

    On the other hand, I believe that EDTA chelation is often given with various nutrients (e.g., magnesium) that may help to protect the brain during chelation.

    Large-scale use of EDTA chelation in children would concern me not only for possible clinically-obvious effects, but potential subtle effects. On the other hand, maybe the positive of chelation would outweigh any risk.

    Anyway, I have included the abstract at the end of this email and would be interested in your thoughts on the subject.

  5. I have read that a significant portion of lead in blood is from recirculated lead that was in the bones (from previous exposure). Do you know if EDTA chelation helps remove lead from the bones?

  6. Are you aware of any nutrients that would tend to reduce the toxic effects of lead or manganese? Or, are their specific nutrient *deficiencies* that would tend to increase the toxicity of lead or manganese.

Abstract Mentioned Above

Duhr EF, Pendergrass JC, Slevin JT & Haley BE

HgEDTA complex inhibits GTP interactions with the E-site of brain beta-tubulin.

Toxicol Appl Pharmacol 122(2):273-280
(1993)

ABSTRACT: "We have found that EDTA and EGTA complexes of Hg2+, which conventional wisdom has assumed are biologically inert, are potentially injurious to the neuronal cytoskeleton. Tubulin, a major protein component of the neuronal cytoskeleton, is the target of multiple toxicants,including many heavy metal ions. Among the mercurials, inorganic mercuric ion (Hg2+) is one of the most potent inhibitors of microtubule polymerization both in vivo and in vitro.

In contrast to other heavy metals, the capacity of Hg2+ to inhibit microtubule polymerization or disrupt formed microtubules cannot be prevented by the addition of EDTA and EGTA, both of which bind Hg2+ with very high affinity. To the contrary, the addition of these two chelating agents potentiates Hg2+ inhibition of tubulin polymerization. Results herein show that HgEDTA and HgEGTA inhibit tubulin polymerization by disrupting the interaction of GTP with the E-site of brain beta-tubulin, an obligatory step in the polymerization of tubulin.

Both HgEDTA and HgEGTA, but not free Hg2+, prevented binding of [32P]8N3GTP, a photoaffinity nucleotide analog of GTP, to the E-site and displaced bound [32P]8N3GTP at low micromolar concentrations. This complete inhibition of photoinsertion into the E-site occurred in a concentration- and time-dependent fashion and was specific for Hg2+ complexes of EDTA and EGTA, among the chelating agents tested. Given the ubiquity of Hg2+ in the environment and the widespread use of EDTA in foodstuffs and medicine, these mercury complexes may pose a potentially serious threat to human health and play a role in diseases of the neuronal cytoskeleton."

**************

Mark D. Gold
mgold@tiac.net



To: add-holistic@mLists.net
From: Roger.D.Masters@Dartmouth.EDU (Roger D. Masters)
Subject: ADD Re: Questions for Visiting Expert

Date: 16 Nov 1999 15:01:57 EST

FOR SIMPLICITY, MY ANSWERS ARE IN CAPS AFTER EACH QUESTION.

> It is my understanding that Tuthill, R.W. put this criticism
> to rest by controlling for socioeconomic factors, thereby showing
> a connection between lead exposure and ADD.
> Is this your understanding of the issue? Are there any other
> recent studies that controlled for socioeconomic status?

OUR WORK HAS CONSISTENTLY CONTROLLED FOR SOCIOECONOMIC STATUS, AND FOR OTHER ECOLOGICAL FACTORS (E.G., THE PRESENCE OF OLD HOUSING, INDUSTRIAL POLLUTION, EDUCATION, ETC. AS WELL AS RACE, AGE, AND SEX). THIS IS TREMENDOUSLY IMPORTANT BECAUSE WE FIND WHAT STATISTICIANS CALL "INTERACTION" EFFECTS: X (FOR EXAMPLE, SILICOFLUORIDE TREATED WATER) IS ASSOCIATED WITH HIGHER BLOOD LEAD IF AND ONLY IF THE CHILD IS IN A TOWN WITH A HIGH PERCENTAGE OF OLDER HOUSING, AND/OR A HIGH FIRST DRAW LEAD LEVEL. THESE INTERACTIONS REFLECT CHEMICAL MECHANISMS IN THE TOXIN (THIS CASE SILICOFLUORIDES) THAT ENHANCE THE UPTAKE OF ANOTHER TOXIN (IN THIS CASE A DIVALENT CATION LIKE LEAD, WHICH THEN CHANGES NEUROTRANSMITTER FUNCTION).

> Are there any steps that families can take to reduce their likely
> exposure to lead? We have many parents on our discussion group
> and any practical steps or ideas to consider would be extremely
> useful.

I KNOW THAT THE ISSUE OF LEAD PAINT REMOVAL IS HOTLY CONTESTED, WITH MANY EXPERTS FAVORING "CAPPING" THE PAINT. THE FIRST AND SIMPLEST DEVICE, AND IT SHOULD BE FOLLOWED *URGENTLY* EVERYWHERE, IS TO PROVIDE CALCIUM SUPPLEMENTS, ESP. ALONG WITH VITAMIN D. UPTAKE OF HEAVY METALS WITH AN IONIC CHARGE OF 2 (THAT IS WHAT IS MEANT BY "DIVALENT CATION" ABOVE) ARE OFTEN SUBSTITUTED FOR EACH OTHER ON THE SURFACE OF NEURONS OR INSIDE THEM; IF CALCIUM LEVELS ARE ADEQUATE, LEAD UPTAKE (OR MANGANESE UPTAKE) IS LOWER OR ABSENT. LITHIUM HAS AN EFFECT LIKE CALCIUM, BY THE WAY.

A SECOND ISSUE IS WATER. USE BOTTLED WATER FOR BABY FORMULA. FILTERS ON FAUCETS. BE ESPECIALLY CAREFUL THE HIGHER UP IN A BUILDING AN APARTMENT IS LOCATED: TOP FLOORS ARE ALWAYS WORSE.

LEAD IN SOIL IS A PROBLEM (THE WORK OF HOWARD MIELKE) BECAUSE LEAD TASTES SWEET, AND KIDS LICK THEIR FINGERS.

>3. Are there any steps that families can take to reduce their changes
> of overexposure to manganese?

AS FAR AS I CAN SEE, THE PROCESS IS SIMILAR FOR LEAD AND MANGANESE.

>4. There are some people who might consider EDTA chelation for
> lead. I am aware a study led by Dr. Boyd Haley of the Univ.
> of Kentucky showing potential adverse effects on the brain
> from EDTA chelation with concurrent exposure
> to mercury (Hg) from food, mercury amalgam fillings, endogenous Hg,

I AM SIMPLY NOT WELL-ENOUGH INFORMED TO MAKE A SCIENTIFIC JUDGMENT

>5. I have read that a significant portion of lead in blood is
> from recirculated lead that was in the bones (from previous
> exposure). Do you know if EDTA chelation helps remove lead
> from the bones?

ASK HERBERT NEEDLEMAN AT U OF PITTSBURGH

>6. Are you aware of any nutrients that would tend to reduce the
> toxic effects of lead or manganese? Or, are their specific
> nutrient *deficiencies* that would tend to increase the toxicity
> of lead or manganese.

SEE ABOVE



To: add-holistic@mLists.net
From: mgold@tiac.net
Subject: ADD Dr. Master's Current Focus
Date: Fri, 19 Nov 1999 20:57:57 -0700 (MST)

Dr. Masters,

You alluded to current interestin your CV related to "neurotixicity associated with pollution, poor diet, and lifestyle risk factors...."

Can you tell us a little bit about this effort? Will it involve new surveys of diet, pollution, lifestyle, and behavior, or do you plan to do a meta-anaylsis of existing scientific literature?

By the way, for everyone else on the group. The work Dr. Masters is doing is very important (in my opinion) in furthering our understanding of the contributing factors to behavioral changes. If any of the organizational representatives or others on the group know of either 1) funding sources for Dr. Masters' foundation or 2) reliable geographic incidence data for ADD/ADHD or Autism, it would be helpful to forward that information to Dr. Masters.

- Mark D. Gold
mgold@tiac.net



To: add-holistic@mLists.net
From: Roger.D.Masters@Dartmouth.EDU
Subject: Re: ADD Dr. Master's Current Focus

Date: 22 Nov 1999 09:41:35 EST

Thanks for your kind words. Our next papes will focus on the risk factors that are linked to lead uptake in the samples of NHANES III and New York: in both cases, we find that silicofluoride water treatment significantly enhances the effect of all risk factors.

A future goal, as soon as we get these papers completed, is to locate and analyze geographic (or time-series) data on such factors as drug usage to treat ADD/ADHD. It has seemed to me that if we can locate such data, it might provide a clear way of analyzing whether environmental toxins play a role in disease incidence.

Let me know if I can be of further assistance,

roger masters