GULF WAR ILLNESS AND GCAQE – NEW DEVELOPMENTS

Malcolm Hooper – PhD, B Pharm, MRIC, C Chem

Emeritus Professor of Medicinal Chemistry

University of Sunderland

GCAQE – MEETING APRIL 29TH 2009 - LONDON

SYNDROMES OF UNCERTAIN ORIGINSMerck Manual 1999, 17th Edition

STRESS - SOMATISATION- PSYCHIATRIC- IN THE MIND

GULF WAR SYNDROME GWI/S = ME of MILITARY

MULTIPLE CHEMICAL

SENSITIVITY

ME-CFSFMS

OPs

NEUROLOGICAL- ANS, PNS, CNSCARDIOVASCULARIMMUNE SYSTEMGASTROINTESTINALRESPIRATORYENDOCRINE SYSTEM

“Considering the extent of the patients’ complaints and disability, the results of ROUTINE laboratory tests were strikingly NORMAL” S Straus

N A P S

CarbOCs

N M

R S

E A

OPs

Pyreth

CWs

E U

V T

RA Dg

BATS

THE MOST TOXIC WAR IN WESTERN MILITARY HISTORYJan. 16 - Feb. 28 1991- [Hooper 2000]

VACCINES

IoM 2000 >40 MAJOR EXPOSURES

USA-UK CONGRESS-PARLIAMENTARY HEARINGS 2000, 2002, 2004, 2008 (RACGWVI (USA-2002, 2004, 2008) AND LLOYD REPORT (UK- Nov 2004)

STRESSORS

PSYCHE EMOTIONS ETC

PHYSICAL/CHEMICAL

VIRUSES BACTERIA, VACCINES

LIGHT , SOUNDELECTRO- MAGNETISMTEMPERATURE

CHEMICALS, OIL/SMOKE, DRUGS, CARCINOGENS

November 2008

465 pages. 1840 references – many peer-reviewed

Findings in Brief

1. GWI and Health of GWVs p.23-56

2. What causes GWI- Effects of Experiences and Exposures. p.59-228.

3. Nature of GWI. p.229-288.

4. Federal Resources GWI and Health of GWVs. p.289-310.

5. Research Priorities and Recommendations. p.311-316.

Executive Summary- 15 pages

A CONGRESSIONALLY-MANDATED REPORT –LORD MORRIS OF MANCHESTER

SYNDROME – ILLNESS – ILLNESSES ?

A MATTER OF DEFINITION

…symptoms are remarkably consistent across diverse GWVs populations. Whether this Gulf War-related symptom complex represents several syndromes, or one syndrome with several subtypes, is an issue of taxonomy ……a consequence of military service, ………only observed in veterans who served in the 1991 Gulf War, p.41

For us GWI = GWS but NOT for MOD (umbrella term)

1. GWI and the Health of Gulf War Veterans

HIGHLIGHTS

GWI is a serious condition multi-symptom condition resulting from service in the 1990-1991 Gulf War, is the most prominent health issue affecting GWVs, but not the only one. p.1 Affects 25-32% GWVs

No effective treatments have been identified …….few GWVs recover over time

Studies consistently indicate that Gulf War illness is UNIQUE not the result of combat or other stressors and that Gulf War veterans have lower rates of posttraumatic stress disorder than veterans of other wars. No similar widespread, unexplained symptomatic illness has been identified in veterans from other war zones

Studies of Gulf War veterans consistently indicate that serving in combat and other psychological stressors during the war are NOT significantly associated with GWI, after adjusting for effects of other wartime exposures…. PTSD rates are LOWER in GWVs…. the large majority of veterans with Gulf War illness have NO psychiatric disorders.

Evidence strongly and consistently indicates that two Gulf War neurotoxic exposures are CAUSALLY associated with Gulf War illness:

1) use of pyridostigmine bromide (PB) pills, given to protecttroops from effects of nerve agents, NAPS.

2) Pesticides, especially OPs- diazinon, chlorpyrifos used during deployment.

CHOLINERGIC AND RELATED NEUROTOXICANTS

An association with low-level exposure to nerve agents cannot be ruled out – Sarin and related compounds but NOT Soman

GCAQE – ROUTINE PESTICIDE EXPOSURE COULD INVOLVE CARBAMATE PESTICIDES- eg PROPOXUR, CARBARYL, BENDICARB etc.

OR PYRETHROIDS eg PERMETHRIN etc- SYNERGISM

CHOLINERGIC TRIPLE WHAMMY

PARAOXONASE

Golomb B. Rand Report,1999- 83 pages of references,

PB cannot be ruled out as a possible contributor to the development of unexplained or undiagnosed illness in some PGW (Persian Gulf War) veterans……...Uncertainties remain concerning the effectiveness of PB in protection of humans against nerve agents……… The use of PB may reduce somewhat the effectiveness of post-exposure treatment for NON-SOMAN nerve agents...

NAPS - PYRIDOSTIGMINE BROMIDE-IND!- CARBAMATE

The issue is a complex one, involving trading off uncertain health risks- but risks now shown to be biologically plausible- against uncertain gains from the use of PB in the warfare setting.

See also Cherry et al 2001

PESTICIDES USED IN GW-1

OPs - DIAZINON, MALATHION, CHLORPYRIFOS, SOME UNKNOWN OPs

CARBAMATES – PROPOXUR, BENDIOCARB

HSE TRAINED OPERATIVE NO PROPER PROTECTION -

PYRETHROIDS LINDANE DEET

SYNERGY DEMONSTRATED CNS DAMAGE TESTICULAR ATROPHY

AGRICULTURE/ FISH CIVILIAN/AEROTOXIC SYNDROME- HIGH USAGE- CONTROVERSIAL INCL. GM HERBICIDES

Abou Donia et al 1996-2002IDENTIFIED AS MAJOR FACTOR AMONG UK GWVs- Cherry et al 2001OEM 2001;58:291-298;299-306.

ACUTE- CHRONIC-DELAYED EFFECTS KNOWN-NERVOUS, ENDOCRINE & IMMUNE SYSTEMS

BASAL GANGLIA-DEEP BRAIN STRUCTURES INCLUDE LENTIFORM

AND CAUDATE NUCLEUS- CONTROL MOVEMENT SEQUENCES

BRAIN STEMTHALAMUS

MID BRAIN

AMYGDALAOLFACTORY

BULB

MIDBRAIN

HIPPOCAMPUS

THE LIMBIC SYSTEM

THE MAJOR SYSTEM AFFECTED BY CHEMICAL EXPOSURES

INFORMATION CENTRES- THALAMUS relay station for SENSORY NERVES BRAIN STEM, SPINAL CORD TO CEREBRUM-PAIN

BRAIN STEM REGULATES VITAL FUNCTIONS-HEART BEAT, RESPIRATION, BLOOD PRRESSURE, DIGESTION, SWALLOWING,

VOMITING etc

VISUAL AUDITORY

FACIAL EXPRESSION EYE MOVEMENT BALANCE

HEART RATE RESPIRATION BLOOD PRESSURE TEMPERATURE SWALLOWING VOMITING

EXPOSURES

MULITPLE

SYMPTOMS

MULTIPLE

SMALLER NUMBER OF MECHANISMS

UNDERSTANDING

IDENTIFIED PATHWAYS CAUSING DAMAGE

NEUROLOGICAL DAMAGE – PERIPHERAL, CENTRAL - DYSAUTONOMIA, ACUTE, DELAYED, OPIDN, CHRONIC,

OPICN

OXIDATIVE STRESS – WIDESPREAD DAMAGE, APOPTOSIS

IMMUNE SYSTEM DISORDERS – REDUCED ACTIVITY- AUTOIMMUNE DISORDERS.

CELLULAR NECROSIS – PRECIPITATE NEW ILLNESSES

LOOK OUT FOR PARKNISONISM, MS, MND(ALS) ?

DIAGNOSTIC TESTS

NEUROPSYCHOLOGICAL – SARAH McKENZIE-ROSS

NEURONAL ANTIBODIES – ABOU-DONIA

OXIDATIVE STRESS – ABOU-DONIA, SPENCE

IMMUNE SYSTEM – NANCY KLIMAS

DYSAUTONOMIA – JULIA NEWTON

ENDOCRINE – INSULIN STRESS TEST STEVE ATKIN

MITOCHONDRIAL FUNCTION –SARAH MYHILL JOHN McLAREN -HOWARD

ADVANCED MRI SCANS – HALEY et al

DECORATED PROEINS ANTIBODIES - FURLONG

TREATMENTS

UNDER INVESTIGATION – RACGWI REPORT

MIDRODRINE – DYSAUTONOMIA

ANTI-OXIDANTS – GLUTATHIONE etc

SARAH MYHILL PROTOCOL – Mg, NIACIN, CoQ 10, D-RIBOSE, N-ACETYL-L- CARNITINE

ATKIN – HORMONE REPLACEMENT – GH-TESTOSTERONE etc

SAMENTO ECUADOREAN HERB - PROMISING NEURONAL RESTORATION

ORGANOPHOSPHATES – PESTICIDES AND OTHERS

GWI/S

FISH FARMING

SHEPHERD

AGRICULTURE

WHEAT STORAGE

FRUIT GROWERS

CREWS

CAQ

PASSENGERS

MoD DEFRA

IN THE WINGS – HERBICDES- GLYPHOSATE, GLUFOSINATE PHOSPHONATES/NERVE AGENTS? – GM CROPS

COMNG FROM LEFT FIELD!!

THE PEOPLE’S PERMANENT TRIBUNAL IN THE HAGUE

The PPT is an international tribunal founded in 1979 in Italy. It uses rigorous conventional court format, and looks into human rights complaints submitted by communities facing abuses. It issues indictments, names relevant laws and documents findings.

It sets out to ensure that agrochemical corporations that produce, distribute and use pesticides are held accountable for the consequences of their actions