Ornithosis

Motto:

"The antigen is nothing, the terrain is everything"- Pasteur

The purpose of this paper is to inquire into the relationship between Al Eskan disease and the probable exposure to chemical warfare agents by Persian Gulf War veterans. Al Eskan disease, first reported in 1991, compromises the body's immunological defense and is a result of the pathogenic properties of the extremely fine, dusty sand located in the central and eastern region of the Arabian peninsula. The disease manifests with localized expression of multisystem disorder. Signs and symptoms of Ai Eskan disease have been termed by the news media "Persian Gulf syndrome." The dust becomes a warfare agent when toxic chemicals are microimpregnated into inert particles. The "dirty dust" concept, that the toxicity of an agent could be enhanced by absorption into inactive particles, dates from World War I. A growing body of evidence shows that coalition forces have encountered Iraqi chemical warfare in the theater of operation/Persian Gulf War to a much greater extent than early U.S. Department of Defense information had indicated. Veterans of that war were exposed to chemical warfare agents in the form of direct (deliberate) attacks by chemical weapons, such as missiles and mines, and indirect (accidental) contamination from demolished munition production plants and storage areas, or otherwise. We conclude that the microimpregnated sand particles in the theater of operation/Persian Gulf War depleted the immune system and simultaneously acted as vehicles for low-intensity exposure to chemical warfare agents and had a modifying-intensifying ef fect on the toxicity of exposed individuals. We recommend recognition of a new term, "dirty sand," as a subcategory of dirty dust/dusty chemical warfare agents. Our ongoing research efforts to investigate the health impact of chemical warfare agent exposure among Persian Gulf War veterans suggest that Al Eskan disease is a plausible and preeminent explanation for the preponderance of Persian Gulf War illnesses.

Introduction

Athough the conduct of the military campaign called the Persian Gulf War was not affected as much by disease as were many previous wars, there have been many cases of service members returning home with continuing medical problems or with unexplained problems arising since their service.'-3 In some cases, family members of returned veterans have also been stricken.4 Cases have been reported from the United States, the United Kingdom, Canada, and other members of the coalition forces.5,6 Although the Arab participants reported no cases,7 the reader is invited to remember that "This campaign took place in a region where freedom of expression is virtually nonexistent."8 The government of the Czech Republic ordered a formal investigation of the illnesses reported by members of the Czechoslovakian Independent Chemical Defense Battalion contingent of the coalition forces, as the Defense Minister of the Czech Republic, Miloslav Vyborny, dismally validated in an interview with The New York Times in 1996.8 Hungary participated with a Military Hospital Professional Staff Increment,9 and after years of latency, cases of Al Eskan disease are being observed in the veterans and in their family members. The government of Iraq held a conference in 1998 on "Postwar Environmental Problems in Iraq as the Consequence of the Coalition Forces' Conduct of the War." Information on the conclusions of the conference is spare, but the fact that the conference took place may support the idea that Iraq's production, storage, and use of chemical/bacteriological warfare may have backfired.

Illnesses of Persian Gulf War veterans have been lumped together by the media and termed Persian Gulf syndrome. Many possible causes are being investigated, but in the wide variety of duty positions and the differing exposures to the various suspect agents, investigators have failed to identify any common exposure to a single causative agent. 10-15 We reported previously that the extent to which a Persian Gulf syndrome can be called a discrete condition, rather than a collection of unrelated medical problems, may be the result of a common exposure to the unique sand dust of the central and eastern areas of the Arabian peninsula. Exposure is often aggravated by various other agents attacking individuals whose immune systems are already compromised. This exposure to the Arabian sand is the one common denominator experienced by all service members deployed to the southwest Asia theater of operation in Operation Desert Shield/ Storm. 16-20 Recent evidence suggests that chemical warfare (CW) exposure may have been nearly widespread. In this article, we reprise the base theory of Al Eskan disease, discuss the evidence of CW exposure among veterans and the action of those agents detected, and consider how the two noxa may operate together if patients are exposed metachronous or synchronous to both.

Al Eskan Disease

Our original and subsequent publications reported a previously unrecognized disease specific to the Arabian peninsula that did not fit traditional diagnostic categories. We observed that during the conduct of the Persian Gulf War, the respiratory problems observed in Al Eskan village near Riyadh, Saudi Arabia, were primarily attributed to the fine, ubiquitous Saudi sand, causing a hyperergic lung reaction with additional symptoms caused by various opportunistic infections or by irritation resulting from other agents in the immunocompromised lungs. We also raised the possibility of a second phase of this disease, resulting both from a continuing compromise of the lung and from fine silicon particles actually entering the bloodstream. We studied the pathogenesis of Al Eskan disease by means of ultrastructural and microanalytical studies of the sand, aerobiological and terrain biocultural studies of the kingdom of Saudi Arabia, and the etiopathogenesis of the disease. We reported the environmental circumstances, symptoms of the veterans, prognosis, treatment, prevalence, and frequency.21-26

We also discussed the most commonly suspected agents in the Persian Gulf syndrome: post-traumatic stress disorder; seasonal diseases; nonseasonal infections; endemic infections; atmospheric pollution; depleted uranium; chemical agent-resistant coating; pesticides and rodenticides; adverse reaction to immunization; side effects of vehicular contamination of immunosera (e.g., squalene, an adjuvant that can speed the immune system); pyridostigmine; calcium content of the Saudi sand; psittacosis; ornithosis; airborne allergic genera; biological warfare agents; and, our special interest in this article, CW agents. It is certain that silicon particles of less than 1 (mu)m average size were present in substantial quantity in the central and eastern regions of the Arabian peninsula, and they were presumed to be inhaled in large quantities. We concluded that each of these factors, including CW agents, are adjuvant or contributing causes. The only common exposure that would lead to the recognition of Persian Gulf syndrome as a single medical condition, rather than an all-encompassing phrase for unrelated conditions, appears to be exposure to the ubiquitous fine sand of the area and a resulting immunosuppression that is aggravated by opportunistic infections and other nonmicrobial ailments. We concluded that by case definition, Al Eskan disease is a multisystem disorder with localized expression(s), based on the body's immune depletion, that is triggered by the bioactive fine sand and enhanced by infectious, environmental organic and inorganic agents, or other noxae, with or without synergism. 16,17,23,24,26-31

Analysis of Physicochemical Properties of the Sand

As part of our effort to assess the health risk from the environment in Operation Desert Shield/Storm, sand samples were analyzed. The purpose of the analyses was to provide a detailed characterization of the particulate matter constituting each sample to be used as part of a detailed human health risk assessment related to the coalition forces. Sampling began in Saudi Arabia in early October 1990, was extended to Kuwait and Iraq during the ground phase of the war, and continued through December 1991. A second set of samples was collected from Iraq and Kuwait between May 10 and 19, 1997. The sand samples were analyzed using scanning electron microscopy, X-ray microanalysis by energy dispersive spectroscopy (EDAM, and X-ray photoelectron spectroscopy. Photomicrographs were taken at different magnifications ranging from 100x to 60,000x. Elemental dot mapping (EDT), which images the site of X-ray emission for a specified element, was also performed. The effective sampling depth of energy dispersive spectroscopy was 0.5 to 1 im for the accelerating voltages used. X-ray photoelectron spectroscopy was carried out with a VG ESCA LAB MARK II system. The effective sampling depth of X-ray photoelectron spectroscopy was 10 to 100 A. The first few atomic layers were probed. Our findings were reported previously.23

At the request of the U.S. Army Surgeon General, the U.S. Army Environmental Hygiene Agency developed a program to determine the magnitude and extent of pollutants released into the atmosphere from the burning oil wells in Kuwait.32 As part of this program, the R.J. Lee Group, under subcontract to the U.S. Army, analyzed sand samples from Saudi Arabia, Kuwait, and Iraq (collected from May to September 1991 and in November 1993) using a variety of analytical techniques, such as atomic absorption spectroscopy, inductive coupled plasma spectroscopy, ion chromatography, gas chromatography, and mass spectroscopy, to document the levels of semivolatile organic compounds, polycyclic aromatic hydrocarbons, halogenated organic compounds, and nitrosamine. The morphology and chemical composition were studied by scanning electron microscopy, transmission electron microscopy, and Fourier-transform nuclear magnetic resonance infrared spectroscopy. Thermo-optical methods were also used to provide information on the organic and elemental carbon components.33 The data obtained from our research and analysis efforts and from those performed by the R.J. Lee Group were compared to provide a comprehensive health risk assessment that evaluated all pathways for routes of exposure to the sand.

In our analysis, the sand grains appeared heavily agglomerated. The grains stacked upon themselves to create fibrous agglomerates with a high similarity to ferruginous bodies. Photomicrographs revealed the average nonagglomerated grain to be in the range of 0.1 to 0.25 (mu)m in 18% of the samples tested. Smaller "free-floating" grains were also present. The grain structure appeared rounded and smooth surfaced. A typical EDAX microanalysis showed calcium to be in a much higher concentration than silicon itself, by a factor of 5 to 1, in our Saudi and Kuwaiti samples compared with sand from other terrestrial areas. Other elements present were magnesium, aluminum, and iron. Spectroscopy showed a peak for potassium; however, potassium and indium cannot be distinguished, and indium foil was used for the mount. The material studied appeared to be a silicate with calcium, magnesium, aluminum, and iron substituted in the crystalline matrix. Some naturally occurring silicates that contain these elements are anorthite (Ca0Al^sub 2^0^sub 3^2Si0^sub 2^), diopside (MgOCa02Si0^sub 2^), akermanite (2Ca0Mg02Si0^sub 2^), monticellite (CaOMgOSi0^sub 2^), feldspars-lime (Ca0Al^sub 2^0^sub 3^2Si0^sub 2^), and kaolin, which is a group of clay minerals such as kaolinite (Al^sub 2^Si^sub 2^0^sub 5^(OH)^sub 4^), and talc (Mg^sub 3^Si^sub 4^O^sub 10^(OH)^sub 2^),23 In most silica minerals, the concentration of Si predominates. Some minerals show a higher concentration of Al, Mg, and Fe, relative to Si, but not in a factor of 5 to 1 (Ca to Si ratio), as is found with the Saudi and Kuwaiti sand samples. If the material in question were a calcium-chlorite composite, there would be slightly more Ca present than Si, but certainly not by a factor of 5. The upper limit of CaO in anorthite is 20%, whereas the lower limit of Si0^sub 2^ is 40%. The natural occurrence of elements in the Earth's crust is approximately 50% 0, 26% Si, and 3% Ca. The concentration of CaO in feldspar is 5%, whereas Si0^sub 2^ is present in an approximate concentration of 65%.

Anecdotal information suggests the presence of sulfur, especially as sulfates, e.g., calcium sulfate dihydrate (gypsum), in the Arabian sand: "When loose sand in a tent peg hole was wetted, it quickly set into a brittle solid, closely resembling plaster of paris" (comment made by a peer reviewer). In our studies, we did not confirm the presence of sulfates, and cited studies also did not report the elemental sulfur concentration. However, one can speculate on the remote possibility that the "dirty sand" (being discussed in this paper in detail) can demonstrate certain aspects of gypsum, polyhalite, and other sulfate minerals; this should be the focus of a separate paper.

The Sahara Desert sand is approximately 88% Si, 2.5% FeO, and 8% CaCO. Palestinian sand is 60% Si, 12.7% CaCO, and 3.4% FeO. Neither Palestinian nor Saharan sand has an overwhelming Ca concentration in its silicate crystallites. The average probe depth of scanning electron microscopy/energy dispersive spectroscopy at 20 kV is approximately 1 (mu)m; it is not the most surface-sensitive analytical technique. Therefore, energy dispersive spectroscopy analysis reveals only bulk characteristics. Elemental dot mapping for Si and Ca did not reveal their respective relative concentrations but did show their strong presence throughout the whole sample. X-ray photoelectron spectroscopy revealed the surface of the Al Eskan sand to contain Al, Ca, Fe, Mg, 0, C, and Si. The C found is an adventitious species. After peak fitting and integration, 0 was revealed to be in the highest concentration, followed by Al. Ca was present on the surface in much less concentration than in the bulk. Qualitative X-ray photoelectron spectroscopy is extremely surface sensitive, so the results reveal only the species residing on the top few atomic layers of the material.

The Mechanism of Gas Stream Particle Separation and Its Correlation to the Human Respiratory System

There are consistent processes through which a particle may settle from a gas stream. The human respiratory system is not exempt from the same dynamic principles affecting innumerable other gas stream applications. The basic methodology is four-fold, however, because other contributory influences exist with respect to specific conditions, both qualitatively and quantitatively. Therefore, focusing on the behavior of particles in a gas stream allows us to show how the human respiratory tract is influenced. Engineering principles dictate that the main influences affecting the outcome of gas stream particle deposition are as shown in Table I. The actual parameters associated with determining each component's influence are complex and beyond the scope of our discussion. Fundamentally, it should be stated that the nature or properties of the particle and the environment are determinant. When one examines the field of influences by magnitude, a few are of a much higher order. Air velocity and particle size seem paramount. This consideration analog with many industrial applications, with the exclusion of radiation. The methodology or mechanisms mentioned as controlling influences are inertial interception, flow-line interception, Brownian diffusion, and sedimentation.

(a) Inertial interception follows Newton's law. A particle of given mass at a relative velocity (relative to the respiratory mechanism) enters the species with each breath. As the upper respiratory conducting system is passed and passage becomes increasingly smaller in diameter, finer impaction occurs, much like in an industrial impingement separator. This mechanism has the greatest effect with higher air velocity.

(b) Flow-line interception occurs as a particle becomes increasingly nearer to the respiratory tract surface at the terminal bronchiole. As a particle arrives at a given distance perpendicular to the flow direction, it is impeded by obstructions and deflected against the wall. By definition, the phenomenon occurs when a particle arrives one particle radius away from the collecting species in a slightly "off parallel" direction.

(c) Brownian diffusion influences the smallest particles (

(d) Sedimentation is based on the most fundamental principles (density and gravity). Specifically, density ratios, gravity, and time affect the outcome quantitatively. Because the relative air velocities are so much lower within the finer respiratory tract, sedimentation represents one of the more prominent mechanisms in the bronchoalveolar portion of the lower respiratory area.

Outside of the methodology, the particle or aerosol concentration gradient is not as much a controlling influence; rather, it is more of a controlling factor. Its significance lies in its ability to increase the total outcome of the deposition mechanism. During a given period, the integration yields a greater amount of deposited solids. Therefore, particle deposition in a laden gas stream is never determined by whether it occurs, but by how much and how fast it is occurring. Categorically, the distinction between dust and fumes is not related arbitrarily. It is based purposefully on size. If a particle's diameter is less than 1 (mu)m, it is categorized as a fume. If a particle is greater than 1 (mu)m, it is categorized as dust. Potential lung-damaging particles are those whose sizes fall in the range of 0.5 to 5 (mu)m.

The influence of each mechanism shifts as the characteristics of the particle and its environment change. There are many order-of magnitude differences in distance traveled by a particle when comparing sedimentation and Brownian diffusion based solely on particle size.

In summation of this corollary to gas stream particle separation, the basic mechanisms are the same as those affecting any other engineering application. The concept of impregnating particles with chemicals to enhance a reaction is not far removed from many current manufacturing techniques. Gas stream filtration is accomplished by the passage of contaminated air over specific agent-targeted absorptive beds. The homeostatic function obviously is not to disinfect the air; however, the transport and deposition mechanics are similar. Our bodies screen contaminants, filter, absorb, and become clogged because of the same causes that affect any gas stream particle separation process.34

Immune Reactions

Studies of human silicosis and experiments with animal models indicate that inhaled sand dust travels through the conduction system of the respiratory tract. The nasal cavity is the first coarse filter. Sand agglomerations are trapped in this area and salvaged from here. The pathological irritation of the olfactory nerve could easily trigger multiple chemical sensitivity.17 The smaller-sized particles (up to 10 (mu)m; dust) and the airbornesized particles (0.1-0.25 (mu)m or less; fume) enter the respiratory portion to the acinus.

The terminal bronchioles' lumen is 0.15 to 0.2 mm in diameter. The individual alveoli measure about 200 (mu)m in diameter. In this "target area," the silica grains, with their long-recognized cytotoxic property, interact with the type I and type II pneumocytes (great cells) as well as with the alveolar macrophages (15-40 (mu)m in size; dust cells). Sand grains smaller than 6 (mu)m can freely float through the pores of Kohn (the pores are 6-10 (mu)m in diameter) of the interalveolar septae and can pass the air-blood barrier by crossing the attenuated pneumocyte (200 A thick), the capillary basement membrane, and the capillary endothelium. The alveolocapillary barrier is about 1.5 /(mu)m, with a range from 1 to several micrometers.

Upon contact, the natural and immune defense mechanisms of the alveolar surface of the lung are activated. The silica grains are engulfed by the alveolar migratory macrophages. These cells have surface receptors for both immunoglobulin G and serum complement. When these substances bind to the silica, particle uptake is enhanced (immune phagocytosis). Noncoated particles can also be incorporated by contact (nonimmune phagocytosis). The engulfed silica resides within phagosomes. Primary lysosomes (about 0.5 (mu)m in diameter) empty a wide range of hydrolytic enzymes into these phagosomes, converting the phagosomes to phagolysosomes. The ergastoplasm and the Golgi complex become stimulated to produce and condense peptides, lysozyme, and interleukin-1 immune interferon. It is suggested that those cells producing cytokines, interleukin-1(beta), and tumor necrosis factor-alpha appear to be intimately associated with the evolving lesions of silicosis, and the lymphoid tissue of the lung may be important in driving the pathogenesis of this disease.35 These secretory products are first carried by the Golgiassociated endoplasmic reticulum and then are delivered by exocytosis to the cell's surface. The peptides invade the resident macrophages and the interalveolar septal dendritic cells, enhancing a T-cell reaction (CD4- and CD8-positive T cells). The peptides convert more naive (virgin) resident macrophages to be committed to silica incorporation. The dendritic cells trap antigens in the presence of the antibody and retain the antigenantibody complexes.36 The dendrites of these cells bind the complexes to their surface membranes. The antigen, relevant to the initiation of an immune response, is processed in tissues by dendritic cells that enter the lymphatic system and drain into regional lymph nodes. Dendritic cells are bone marrow-derived cells with some features of monocytes and macrophages (morphologic similarity), but they are quite distinct in other ways. Dendritic cells are nonphagocytic, only loosely adherent, and constitutively express high levels of class II major histocompatibility complex antigens. It has been proposed that tissue dendritic cells carrying processed antigen from the periphery lose the capacity to process new antigens in the lymph nodes but acquire a unique capacity to stimulate naive T cells.37

The chemotactic attraction of the cellular and humoral immune system also activates an alternative pathway of complement components, as shown in Figure 1. The immunoproducts are discharged to the pulmonary vein, with the result of hypergammaglobulinemia. Upon the interaction of silica grains with type II pneumocytes, cellular hypertrophy, hyperplasia, and increased production of phospholipids identical to the surfactant have been observed.

In the phagolysosomes, silicic acid is produced. The silicic acid has the potential to attack the phospholipid layer of the cell's limiting membranes. The ingested silica also raises the intracellular peroxidase level. Peroxidase and silicic acid can harm membrane constituents. Partial dissolution of the membranes causes liberation of hydrolytic enzymes, resulting in necrosis and subsequent cell death. Silica particles can exert various cytotoxic suppressive effects on macrophages, such as depression of phagocytosis, and, in turn, ineffective microbicidal responses of the silica-laden macrophages. It may lead to an uncontrolled spread of opportunistic infections, e.g., Mycoplasma incognitos, and could intensify the effects of sublethal exposure to biological warfare agents, e.g., mycotoxins. Inactivation and degradation of ingested microorganisms by macrophages and granulocytes are crucial to host defenses against infection. Macrophages participate in host defenses through direct inactivation of microorganisms and participate in immune responses. The antimicrobial capacity of macrophages can be compromised by the blockage of the mononuclear phagocyte system, formerly termed the reticuloendothelial system. This blockage can be caused by previous engorgement of macrophages with ingested material after phagocytosis. Silica particles, coated by or in conjunction with immune proteins, form an antigen. The antigen, and in turn, the silica, become detectable by monoclonal clone techniques.

The smooth rounded surface seems to promote an unchallenged passage of the sand particles all the way down to the target area: the reticuloendothelial system at the alveoli. Fibrogenicity is another important pathogenic characteristic of the sand. Silica particles less than 1 (mu)m are believed to be most pathogenic. The size of silica particles retained by the human lung is remarkably constant, 0.5 to 0.7 (mu)m. The initial early lung lesion is an extrinsic hyperergic alveolitis adjusted by cellular and humoral immune complexes and complementary binding complexes. Subsequently, a fibrosing macrophagic alveolitis develops around the dust deposits. It is microscopic in extension and can lead to a nodular or a linear (diatomite) fibrosis of the pulmonary stroma.23,38-45 Table II demonstrates the pathomechanism of Al Eskan disease, with special emphasis on the double bailiwick of CW agents.

CW in the Theater of Operation

Mauroni46 states that, "Yet because the Army had ignored nuclear biological chemical [NBC] defense training, equipment modernization and leadership development for decades many veterans continue to see CW agents as a likely cause of Persian Gulf syndrome because of ignorance, not because of fact." Here, we conclude that the facts are in favor of many veterans' beliefs.

By definition, CW agents are "chemical substances, whether gaseous, liquid, or solid substance, which might be employed because of their direct toxic effects on men, animals and plants."47 Consequently, chemical weapons are those weapons capable of disseminating CW agents.

General H. Norman Schwartzkopf, a brilliant military strategist, as Commander in Chief, Central Command (US-CENTCOM), one of six U.S. multiservice commands, considered the CW threat extremely grave. He planned to cope with the CW threat at several different levels. In planning for possible casualties of 10,000 to 30,000, he professed that, "The possibility of mass casualties from chemical weapons was the main reason we had sixty-three hospitals, two hospital ships, and eighteen thousand beds ready in the war zone."11 The tempo of his conduct of the ground phase of the war may remind one of the Third Reich's blitzkrieg; it possibly saved hundreds of thousands of coalition forces members from annihilation by poisonous gas. Avoiding mass concentrations of troops and maintaining a rapid tempo minimized the effective use of CW agents on the forces. The unrolling history of this war testifies that that general, besides securing victory, successfully negotiated the lives of hundreds and thousands of his soldiers out of the jaws of a horrifying death. The U.S. Army Medical Department, however, had made limited provision for the treatment of CW agent casualties, and there were gaps in biological warfare (BVI) defense, primarily in the area of early, rapid detection and warning. 16,17,23

Whether the coalition forces had any exposure to CW agents is debated extensively and remains as controversial as the quantity and quality of the exposure.` Possibilities of exposure, without any attempt to prioritize, include the following.

(a) Although the Pentagon declared that it had air raided and destroyed Iraq's CW agents production sites and CW weapons storage bunkers by the careful timing of attacks and choice of ammunition, these raids may have released plumes of CW agents to drift toward coalition forces-held territory.48-50

(b) The demolition of Iraqi ammunition bunkers and the destruction of marked and unmarked CW weapons may have caused accidental release. The most eclat example is reflected in the reports available about the Khamisiyah ammunition depot's destruction between March 4 and 15, 1991. We discuss this incident below under the subheading "Tangibility of CW Agents in the Theater of Operation."

(c) Iraqi forces might have used air-, ground-, or sea-delivered CW agents during the campaign. An example is the incident that occurred on January 19/20, 1991, at Port al Jubayl, Kingdom of Saudi Arabia. We note that Lieutenant General C. Homer, the Joint Forces Air Component Commander, mentioned in his congressional testimony that as soon as intelligence sources indicated that medium-range bombers were being loaded with chemical weapons at Al Taqaddum, Iraq, Fl 17A Stealth aircraft were promptly reassigned to destroy six of these aircraft on the ground. However, there is no evidence that there were no other aircraft.48,.51,52

United Nations Special Commissions Inspector Teams (UNSCOM found that Iraqi "quality control" was so poor that Iraq's CW agents were only 50 to 60% effective after being poured into missile warheads and artillery shells, which added a factor in favor of the assumed "low-density" CW agent exposure. Eddington noted that, "Postwar UNSCOM inspections revealed that while Iraqi nerve agents had degraded by 90% or more, Iraqi mustard agent was 90% pure as of late 1991."8 The imminent danger of bacterial and chemical warfare (BCW) agents was known to the troops of the coalition forces before entering the combat area, and service members were trained to take countermeasures.53 Changes to the U.S. Army Chemical Corps doctrine in 1980 resulted in the doctrine and training change from a Chemical Corps concern to an Army-wide concern. The operational emphasis changed from the minimization of chemical casualties to minimizing mission degradation; the degree of acceptable risk changed from zero to intelligent risk; the control of chemical defense operations changed from centralized under division NBC element to decentralized, and flexible at the brigade level; the decontamination operations changed from complete decontamination of troops and equipment to partial decontamination (enough to continue the mission).

Although evidence existed that Iraq had BCW agent capacity, intelligence reports had concluded that there was no intention to use it. That information was accepted at face value and may have corrupted our research on the cause, understanding, and cure of Persian Gulf War illnesses for a time.23,52,54 However, contrary to early reports of the U.S. intelligence community, the Czechoslovakian Independent Chemical Defense Battalion contingent of the coalition forces (contracted to the Kingdom of Saudi Arabia to support Saudi forces only) did detect nerve agent (sarin) on January 19, 1991, and mustard nitrogen on January 24, 1991, in the area and vicinity of Wadi al Batin as well as in King Kahlid Military City (KKMC) within the military encampment in which the units were billeted.55 The Czechoslovakian contingent was deployed with 61 vehicles (AL-1 mobile laboratories, ARS-12 M decontamination vehicles, and UAZ-469CH NBC reconnaissance vehicles; the UAZ-469CH was due to be replaced because it was found to provide inadequate protection against CW agents as well as against small-caliber weapons and splinters) and initially had 169 personnel, one of whom shot himself dead on January 16, 1991; it was later augmented by 30 soldiers on February 5, 1991. This contingent was required to provide chemical reconnaissance, treat any CW casualties, and organize courses on CW instruction for the Kingdom's troops. The battalion's four task forces were placed in charge of NBC reconnaissance in KKMC, attached to the Saudi Army's field hospital near the town of Hafar al Batin, and assigned to the 4th and 20th Saudi Mechanized Infantry Brigade, respectively.57 British and French forces, from a greater distance at their tactical assembly areas, also reported CW agents (sarin, tabun, and mustard nitrogen) in sublethal quantities.s6s Eddington8 cites many examples of low-level detections by U.S. forces as well, with most declassified reports recovered from the U.S. Marine Expeditionary Force.

Wadi al Batin has its military interest. Historically, military campaigns from the north (Mesopotamia) were conducted using this Wadi to invade the Arabian peninsula. To protect the country, the Kingdom fortified the bottleneck of the Wadi known to us as KKMC. By 1976, the U.S. Army Corps of Engineers was overseeing nearly $20 billion in military construction in the Kingdom of Saudi Arabia, including three entire military cities: KKMC to the east, Tabuq to the northwest, and Khamish Mushayat to the southwest. Port facilities were also expanded at Ras al Mishab, Jidda, and al Jubayl. Upon the Iraqi invasion of Kuwait, the Corps of Engineers returned to construct additional facilities at al Jubayl to accommodate the coalition forces' deployment. Logically, these sites were preordained as primary on the Iraqi strategic target list. The reader's attention is directed to the incident that occurred on January 19/20, 1991, at Port al Jubayl. 12.48,51.52,58,59

Owing to the peculiar nature, especially the microscopic size, of the granules of the Saudi sand, it cannot be used for cement production. The Kingdom had to import sand for the construction work. We reported the presence of odd sand samples from KKMC and its immediate vicinity.16,21 This observation opened the door for speculation that Iraq exported CW agent-saturated sand for the construction work to sicken or destroy the military cities' population, an action that could remain immaculately unsuspicious in the eyes of the Arab brotherhood. Iraqi military doctrine recognized and incorporated the effectiveness of continued low-level exposure to CW agents against the country's adversaries. Tucker, in his report to the Subcommittee on Human Resources and Intergovernmental Relations, Committee on Governmental Reform and Oversight, U.S. House of Representatives, referred to an Iraqi Air Force academic manual entitled "A Course in NBC Protection" that stated that CW nerve agents have a cumulative effect. If small doses are used repeatedly on a target, the damage can be very severe.60

The Dirty Dust: Absorption of Gaseous or Liquid CW Agents by Particles

The caprice of dirty dust dates from World War I. It was put forward again during the Iran-Iraq War, when CW agents were used on a large scale, and then again, we believe, in the Persian Gulf War.

In an attempt to increase the persistence of phosgene under field conditions, German scientists studied the physicochemical properties of mustard nitrogen-impregnated inert particles. Mustard gas has a low volatility and therefore can persist in the field as an effective agent for days to weeks after dissemination, with the length of time depending on climatic conditions.61 It was observed that in addition to the extended lifetime, which was achieved through the microimpregnation of the agent into solid particles, the toxicity of sulfur mustard could be enhanced by the presence of submicronic inert carbon-black particles. Lefebure62 recorded that a prisoner of a German gas battalion had reported the use of pumice granules impregnated with phosgene.

Comparing our studies of the sand particles in AI Eskan disease with reported results using the impregnation, it is safe to conclude that the effectiveness of CW agent absorption into sand particles would be enhanced by the following.

(a) Poisoning the first respiratory filter system, the upper respiratory trunk, and, by the extended presence of CW agents in the lower respiratory trunk, the alveoli. This could produce tissue damage as well as increase the duration of tissue exposure to CW agents at the alveolocapillary barrier.

(b) By dust particles encountering the body's first fine of immune defense (alveolar macrophages), the macrophages would experience the direct toxicity of the substance and become bioactive vehicles by depleting the engulfing capacity at the alveolar level, which, in turn, would compromise the immune defense mechanism.

(c) The CW agent-saturated submicron-size particles would also penetrate the alveolocapillary barrier, entering the bloodstream, to be disseminated via the lymphatic and blood vessels.

(d) Contrary to the view that absorption of toxic gases by submicron particles without subsequent release would be expected to reduce the agent's toxicity indiscriminately, their impregnation to bioactive particulate matter, sand granules in this instance, would readily increase their toxic effects.

Tangibility of CW Agents in the Theater of Operation

The U.S. Defense Intelligent Agency's (DIA] pre-ground-war reckoning stated that, "DIA assessed that in the Kuwait Theater of Operation (KTO), the CW [agent] stockpile was likely distributed to the general support ammunition depots having chemical storage bunkers, as well as field supply areas for the deployed units."77 Whether Iraq possessed CW agent-impregnated dust (dirty dust] and whether the sand particles were used as a vector remains a matter of dispute.78 The probability is worth considering in some detail.

What we do know:

- that Iraq had unrivaled recent combat experience in using such agents, both offensively and defensively61;

- that Iraq's CW agent production was headquartered at the state establishment for pesticide production at Al Muthanna, near Samarra, north of Baghdad;

- that the ingredients for CW agents were imported by Iraq and also manufactured at Habbaniyah, west of Baghdad-, - that CW agents were inserted into bombs, artillery shells, and rockets; and

- that Iraq dispersed equipment for the production of CW agents throughout the country and stockpiled CW weaponry in 20 to 30 known storage sites. Ar Rumaiyah was a CW storage complex located in the rear of the Iraqi Republican Forces command, and another was located just south of An Nasiriyah and approximately 25 miles north of Basra, the Khamisiyah complex.

Iraq produced the following major CW agents: mustard gas, "khardel" by Iraqi nomenclature, also called Yperite. (It was used on the night of July 12, 1917, at Ypres .79 The name mustard was given to the compound by soldiers during World War I because of its smell.) There are several mustard nitrogens. Those of relevance here are the blister agent H [mustard gas, Yperite, sulfur mustard, Kampfstoff Lost 1, l'-thiobis(2-chloroethane)], the HNI [N-ethyl-2,2'-di(chloroethyl)amine], the HN2 IN-methyl-2,2'-di(chloroethyl)amine], and the HN3 [2,2',2"-tri(chloroethyl)amine]. Iraq also produced the nerve agents tabun (GA [ethyl N-diinethylphosphoranlidocyanidatel), sarin (GB [isopropyl methylphosphonofluoridate]), and cyclosarin (GF [cyclohexyl methylphosphonofluoridate]). Iraq also was to develop soman (GD [pinacolyl methylphosphonofluoridate]), a persistent nerve agent, VX [(0-ethyl-S-(2(diisopropylamino)ethyl)methylphosphonothioate], and the superhallucinogen, a standard incapacitating agent called BZ (3-quinuclidinyl benzilate; a-hydroxy-a-phenylbenzeneacetic acid; 1-azabicyclo(2,2,2)oct-3ylester; alternatively 3-quinuclidinyl benzilate) or EA 2277,80 and CW agent 15.81 Iraq is believed to have possessed the CW mental incapacitant since 1980. Our knowledge of CW agent 15 itself is limited. It belongs to the group of glycolates (esters of glycolic acid). A prominent member of the glycolates group is the BZ agent. The pathophysiologic mechanism of the group is cholinergic nerve transmission blockage in the central and peripheral nervous systems by an anticholinergic effect.

Marrs and his colleagues argue that with sarin and mustard gas, in this instance, which act systematically and do not produce their effects by damaging the lung, little is likely to be gained by absorption onto particles. In addition, dilution of toxic material with particles inevitably reduces the weapon payload of that toxic material. Our investigations presented here cannot confirm this opinion. To the contrary, the absorption of CW agents onto particles (inert or bioactive) can advance, modify, or alter their action and, most importantly, can camouflage their presence with fatal consequences of nonrecognition.

Iraq's delivery systems included 122-mm multiple rocket launchers, helicopter-launched 90-mm rockets, 250/500-kg bombs, projectiles for 155-mm artillery pieces, 120-mm mortals, and SCUD missile warheads.82 The SCUD is a Russianbuilt SS-1-type surface-to-surface guided ballistic missile, copied from the German Third Reich's V^sub 2^ and designed in the 1950s. It is powered by a storable liquid propellant motor (single stage), has a range of approximately 300 km, and carries a conventional warhead of approximately 1,000 kg. Although originally transported on a "Josip Stalin" heavy tank chassis, the SCUD-B is primarily mounted on a transporter-ejectorlauncher vehicle based on the MAZ-543 (8 x 8) wheeled chassis. Unlike unguided missiles, the SCUD has movable fins. The Al Hussein is the Iraqi version of the SCUD missile. It has a longer range, about 750 km, but a smaller payload by weight, not by volume, than the original SCUD. The target acquisition accuracy is measured in square kilometers. The SCUD modified B and C versions (Hwasong [translates to Marsh]) 5 and 6 have an improved range of 340 to 500 km and a decreased warhead weight of 770 to 700 kg. These figures are based on the best "open-source" information currently available and should be regarded as provisional.

Iraq also possessed 40 and possibly 52 Italian-made Mistral-2 aerosol generators with a military potential to disperse CW agents, liquid or solid, even when mounted simultaneously on remotely piloted MiGs (MiG is the Soviet designation for aircraft from the Mikoyan-Gurevich design bureau). They were custom built to be loaded from 55-gallon drums and to deliver chemical or chemical/bacteriological "cocktail" agents approaching 800 gallons per hour through adjustable nozzles to different particle sizes and could be rotated up and down in 180 degrees. The Iraqi Air Force Swiss-made turbo propeller-driven Pilatus planes had been used to deliver CW agents during the Iran-Iraq War and were based at Umm guasr Arabs near Basra. Air bases at Tallil, Al Jahrah, Shaibah, Al Taqaddum, and Balad were reported to be CW agent storage sites. The U.S. Department of Defense (DOD) examined the possibility that an Iraqi patrol boat or a low-flying aircraft may have been involved in the attack on al Jubayl.12

We also became aware that Iraq was preparing its ground forces for combat in a chemically contaminated environment in the KTO. Thirteen CW ammunition storage areas and at least 24 decontamination sites were identified in southern Iraq, where any soldiers, vehicles, and equipment could be decontaminated if caught by their own gas in unfavorable winds, temperature, or rain, or in their combination.84 Specific reports are available that suggest that the Iraqi Third Corps was preparing to use chemical weapons.85.86

During the Persian Gulf War and before, Iraqi forces followed the Warsaw Pact (Soviet) doctrine, with customization to fit their specific circumstances. Accordingly, authorization to launch NBC strikes was held at the highest possible command level: Supreme Commander in Chief, Saddam Hussein, in this instance, Headquarters of the Supreme High Command (an adaptation of the Soviet "STAVKA" ).87 NBC-independent battalions with delivery systems but without NBC ammunition were deployed to the division's sector of operation. They remained inorganic assets to the division commander until directed otherwise. NBC ammunition would be stockpiled in storage facilities with special vehicles and NBC escort personnel to accompany movements; these were designated to transport the warheads from the production facility to the forward predisposition sites and from there to the delivery systems, located with the NBC battalions.88 Although Iraqi documents and enemy prisoner of war reports are available indicating the marking of CW ammunition with a color-coded ring system or a colored skull-and-crossbones scheme, consequent to Iraqi doctrinal practice, there was no need to mark the munitions, because most were made to be used shortly after production. Again, by Warsaw Pact NBC doctrine, "to tie up more resources and surviving personnel and slow the tempo," support areas and units in the rear were to be priority targets. As a result, an NBC strike was not left at the discretion of field commanders until ordered otherwise. CW munitions could still prove useful as a force multiplier on the battlefield to protect the flanks and disrupt enemy operations in the rear. The cumulative effect of sublethal doses of CW nerve agents used repeatedly on targets, resulting in severe incapacitation and long-term casualties, was taken into strategic consideration by Iraq. The use of nerve agents at night, for example, would increase their persistence and enhance their nonlethal incapacitating effects, miosis being a case in point. Iraq had approximately 4 months for prepositioning and concealment of CW agents during the buildup phase of the war and thereby preserved from destruction about 50,000 filled munitions, including 28 ballistic missile warheads loaded with sarin, 13,000 155-mm shells loaded with mustard gas, 6,200 rockets loaded with nerve agent, 800 nerve agent-filled aerial bombs, 90,000 unfilled munitions, and 750 metric tons of CW agents and stocks of thiodiglycol, a precursor chemical for mustard gas; these resources were eventually declared to UNSCOM.? It is reasonable to believe that Iraqi CW agents and munitions alike were repositioned in the KTO before the air phase of the war, and not subsequently. The "buildup time" from the invasion of Kuwait to the beginning of the air phase of the war was approximately 4 months. A common belief is that this window of opportunity to prepare the theater of operation was not secured by the coalition forces, but a given by Iraq as a strategic miscalculation. It seems logical to suppose that it was not a strategic mistake of Iraq but rather a need to prepare KTO as an offensive CW battlefield by prepositioning CW and BCW agents at supply and distribution points. The bombing rendered the Iraqi infrastructure incapacitated. For example, Iraqi authorities reported the destruction of 83 road bridges in Iraq by bombing strikes.90 The coalition forces' intelligence network intercepted Saddam Hussein's orders to release CW agents to the corps and division levels. The neutralization of the Iraqi command, control, and communications would have rendered the field commanders incapable of issuing orders to distribute CW agents from their storage depots. This may also have resulted in an uncoordinated, piecemeal use of the CW agents by lower-level commanders, with or without authority.

Using area reconnaissance photographs, the U.S. Central Intelligence Agency (CIA) identified approximately 30 bacteriological/chemical warfare (BCW) storage bunkers, 4 of them near Salman Park. The Khamisiyah ammunition depot was also pointed out by the CIA because of the detected traffic of special vehicles to and from the depot, the special build of the bunkers, and the air conditioning system (since 1986).91.92 The CIA mapping has been criticized, and efforts have been made to invalidate it. The Khamisiyah ammunition storage area (also labeled in different reports as Tall al Lahm and Sug al Shugukh after nearby villages), about 20 km southeast of Nasiriyah itself, is approximately 50 km2, with about 100 ammunition bunkers, special types of storage buildings, open pits, and buried ammunition dumps. Iraq moved nearly 2,000 unmarked, 122-mm nerve agent rockets from Al Muthanna to Khamisiyah immediately before the air campaign. The rockets were moved subsequently from the bunkers to open pits because of their instability (they were leaking already upon arrival). After the war, UNSCOM discovered that in late 1991, 90% of the mustard gas agents remained stable, then the nerve agents degraded by up to 90%.93 This would suggest that any residual CW contamination would most likely come from blister agents than from nerve agents, with the possible exception of cyclosarin. On February 26, elements of the U.S. Army's 24th Infantry Division occupied the Hhamisiyah area. At the conclusion of the ground war, the U.S. Army's 82nd Airborne Division took over the Khamisiyah bunker complex. By order of General Schwarzkopf, Army Central Command (US-ARCENT) initiated the demolition of thousands of tons of ammunition there." On March 2, the 937th Engineering Group tasked this demolition to the U.S. Army's 37th Engineer Battalion, elements of the 307th Engineer Battalion, and the 60th Ordnance Detachment (Explosive Ordnance Disposal) as well as other supporting personnel: firefighters, technical intelligence teams, and a Civil Affairs Detachment, for a total of 430 personnel. It is a reasonable assumption that the demolition units detonating the Khamisiyah bunkers were not aware of the CIA records. From March 4 to 16, the demolition teams rigged each bunker with explosives, including bunker 73, which later was marked as housing CW weapons by the UNSCOM inspectors. Although records reveal that M8A1 alarm kits went off right after the explosions, no casualties or signs of health problems were reported, or none that were available to the authors, at least. Enemy ordnance demolition operations continued at An Nasiriyah, at Tallil, and at other munition stocks discovered in southern Iraq. When the U.S. Army's XVIII Airborne Corps turned over the area to the VIIth Corps, the 2nd Armored Cavalry Regiment did reconnaissance the Khamisiyah area bunkers for BCW ammunition, with negative findings. Contrary to this report, UNSCOM inspectors identified three areas at Khamisiyah holding CW weapons. Postaction CIA computer simulations suggested that by destroying the production facilities, storage sites, and ammunition bunkers, a number of coalition forces personnel were exposed to low-density CW agents. The estimated number ranges from 80,000 to 100,000 or more, depending on the source.?995 The CIA model did not count on the rapid vertical spreading near the simultaneously detonated bunkers [37 at once, including the suspected bunker 73) to an altitude of 800 to 1,200 m, so that the plume may have spread all the way to the top of the convective boundary layer on that day, March 4, 1991. The CIA model used a 15-m height for the explosive plume and also discounted any atmospheric turbulence caused by the hot desert midday.

In addition, during the war, the night (dawn) bombing of Iraqi BWC agent facilities was under stable atmospheric conditions at first, but the prevailing wind of north-northwest shifted to south-southeast (these winds are the weather patterns of the Mesopotamian valley and the central and eastern region of the Arabian peninsula) and would have blown plume farther. This condensed, hydrated plume could have easily saturated the sand at remote distances upon fallout. Sarin is water soluble, and increasing its pH with rainwater has an intensifying effect on its toxicity.

Although Iraq denied using nerve agent VX, recent investigations tend to contradict this. Fragments of a SCUD warhead were studied in three independent and reputable laboratories in the United States, Switzerland, and Sweden. Although the U.S. laboratory reported elements of a VX precursor, the two other laboratories could not confirm it. The Swedish laboratory, however, detected remnants of decontaminants on the fragments, raising the possibility of an Iraqi attempt to tamper with the samples. In fact, it is known that Iraq manufactured 200 metric tones of VX and cannot account for it. Intelligence reports suggest that Iraq had the capacity to convert VX to solid salt formations for storage and later use.

US-CENTCOM's Air Force component (9th Air Force HQ) attacked BCW agent production and storage sites during the air phase of the war before dawn, intending to allow the sun to evaporate the agents again; if the plumes reached the top of the convective boundary layer of the atmosphere, that would have the unintended consequence of creating fallout at far remote areas. In either case, when the low-density CW agents settled on the ground, it could create dirty dust by saturating the ab ovo specific sand, with its pathogenic properties characteristic of the central and eastern region of the Arabian peninsula.2s.ss

According to the Pentagon's later assessment, at least two of the seven Czechoslovakian and French detections were credible (one nerve agent, one mustard agent). In all of the creditable cases, the amount of agent detected was determined to be without military significance, less than 0.04 mg/min/m^sup 3^. de la Billiere claims that of more than 30 suspected BCW agent production and storage areas, only 2, Al Muthanna and Al Muhammadiyat, sustained serious enough damage to release BCW agents by the bombing campaign in February 1991.97 At Al Muthanna, approximately 16.8 metric tons of sarin/cyclosarin mix was hit, and at Al Mahmudiyah, approximately 15.2 metric tons of mustard agent and somewhat less than 3 metric tons of sarin/cyclosarin mixture was hit.

Based on past U.S. tests, all except 2.5% of the CW agent in a bunker would have been degraded by the heat from the explosion and other burning debris. We agree with Eddington that this assertion is highly dubious. As the Persian Gulf War demonstrated, direct hits on bunkers did not always destroy all of the munitions within or incinerate the CW agent. This is because an attack with a single high-explosive weapon is not equivalent to sustained hydrolysis. The nature of the damage to a given bunker may preclude significant munitions destruction, e.g., by the structure collapsing and burying munitions rather than destroying them, but can instead free CW agents into the air. Similar less-than-optimal results are likely to have occurred with the postwar demolition of munitions.

The An Nasiriyah bombing on January 16, 1991, was followed by an immediate windy rain storm directed toward coalition forces-held territory, and any hydrolyzed sarin clouds could have saturated the sand up to 150 to 200 km downwind, creating low-level exposure or "dirty dust." The recorded heavy winds and inclement weather, which set a 10-year record for rainfall in the region, possibly were not accounted for when the DOD, Defense Nuclear Agency, Defense Science Board, U.S. Army, CIA, and Presidential Advisory Committee on Gulf War Illnesses all concluded that no U.S. service members were exposed to CW agent from the fallout of bombed CW production/storage facilities or CW weapons.989

For the clarity of terminology, we want to state that the "yellow dust" characteristic of dried mustard gas and used by Sovietsupplied insurgents in Laos matches in appearance the yellow dust that coated tents and outdoor coats in the KTO. It seems paramount to note that the "dusty mustard" (yellow dust) also falls into the category of dusty CW agents. The so-called `white dust" could easily be produced by the incinerated depleted uranium rounds' and could have formed a dusty white ash-like substance that covered the target vehicles and their surroundings, producing a new and radioactive category of dirty dust.

BW Agents in the KTO

Although the primary focus of this paper is the consideration of the ample body of new evidence concerning Iraq's use of CW agents, the possibility of coalition forces being exposed to BW agents must also be considered. Following the Warsaw Pact (Soviet) doctrine of mixing BW and low-dose CW agents, the resulting cocktail (also called nouichock in Russian nomenclature) may make these invisible munitions much more difficult to detect and defend against. The "yellow rain" was caused by a biological substance called Tricothcene mycotoxin (Mycologia, Deuteromycotina, Hyphomycetales, Tuberculariaceae). Mycotoxins are chemical compounds produced by fungi. Aflatoxins are a type of mycotoxin produced by Aspergillus flaus. They were researched in the Soviet Union and its satellite countries. An example is the liver toxicity research project at the First Pathology and Oncology Research Institute, Semmelweis Medical University, Hungary, in the late 1960s and early 1970s, in which the researchers were kept blinded about the true nature of the compound aflatoxin and its military application. There is evidence that Iraq possessed this mycotoxin before the war and used it against coalition forces. Reports indicated a yellow precipitation after the al Jubayl attack on January 19/20, 1991.8,48,51 A deliberate nouichock attack against coalition forces ideally suited Iraqi Soviet-assisted war-fighting doctrine.89 A cocktail of slow-acting BW agent(s) and low-intensity CW agent(s), with the modifying component of impregnation into sand particles, may cause debilitating maladies in nonnatives of the Arabian peninsula with an already immune-depleted health status. Tuite reported that the Lawrence Livermore National Laboratory Forensic Science Center found unique DNA sequences for 9-fever and Brucella plagues on gas mask filters used in the war, indicative of a genetically altered BW agent.48 UNSCOM inspectors found evidence that Iraq conducted research on enhancing the pathogenetics of Bacillus antracis, B. ceres, B. megatillus, and B. subtilus, Clostridium botulinum C. perfringens, and C. tetani, Brucella abort and B, melitensis, Francisella tularensis, Escherichia coli, and Histoplasma capsulatum.59

Discussion

At the conclusion of the Persian Gulf War, the DOD standpoint was that CW weapons were not present in the KTO. After an investigation triggered by the CIA disclosure in 1994 that CW weapons were found at the KTO, on November 12, 1996, the U.S. Deputy Secretary of Defense established the Office of the Special Assistant for Gulf War Illnesses (OSAGWI). OSAGWI and its predecessor, the Persian Gulf Illnesses Investigating Team, were charged with investigating possible exposures of service members to BCW agents. OSAGWI methodology follows the standards of investigation of the United Nations and the international community. Each investigation results in a so-called case narrative document. The assessment concludes in terms of "definitely," "likely," "indeterminate," "unlikely," or "definitely not" on the likelihood of exposure to CW agents. Although OSAGWI is attempting to restore DOD credibility among veterans in its effort to determine the cause of the Persian Gulf War illnesses, its success is so far impaired by a failure to correlate findings of possible CW agent exposure with the health problems of individuals involved in the investigated incidents. The systematic use of the DOD's Comprehensive Clinical Evaluation Program and the Department of Veteran Affairs' Gulf War Health Examination Registry, although limited by participation bias, could enhance OSAGWI's mission completion significantly.12

We had previously concluded that CW agents can be regarded as adjuvant factors in Al Eskan disease, albeit some are potentially more harmful than others. Infectious disorders, atmospheric pollution, depleted uranium, pyridostigmine, and seasonal disease, for example, are most of the commonly suspected agents in the Persian Gulf illnesses (Table II).16,17 In Al Eskan disease, several cytokines recruit activated immune and inflammatory cells to the site of the lung. These activated cells produce many other mediators of inflammation. This ailment results from an interaction of genetic and environmental factors. Genes, such as in silicotic rheumatoid arthritis (also called rheumatoid pneumoconiosis, or Caplan's syndrome), lupus erythematosus, scleroderma, renal glomerular disease, and polymyositis may determine the patient's susceptibility to the disease and the disease's potential severity, but environmental factors such as dirty sand may be a major determinant of its course.

Once established, Al Eskan disease appears to have a momentum of its own. The depletion of silica by chelation would prevent end-organ damage and would improve survival both in patients with autoimmune manifestations of Al Eskan disease and in patients with acquired immune disorders; survival rates, however, will be altered by microbial or nonorganic environmental toxicants, e.g., CW agents. Similar to the chelation therapy of other toxicants, our working hypothesis is that patients who receive effective silica reduction therapy before the development of phase II of Al Eskan disease presumably would have a normal life expectancy, whereas the life span of patients who have developed Al Eskan disease phase II before treatment begins would be greatly decreased. Our assumption regarding the beneficial therapeutic effect of the chelation therapy is supported by our previous observations: agricultural toxic agents in the bispiridinum family (e.g., paraquat, gramoxon, 1,1'-dimetil4,4'-bispiridinum diclorid, a potential blood agent) are not absorbed by active carbon in the protective suits, but a protective colloid, montmorillonit bentonite), may be able to absorb them. It is also noted that chromosome aberrations were prevented by montmorilonit. The chromosome aberrations are triggered by the side chain's alkalic nitrogen groups in immunocompromised experimental animals.

The genetic differences in susceptibility to environmental noxae are conspicuous, and the search for particular gene sequences that may correlate with hypersensitivity is ongoing. The significantly high incidence of tuberculosis in populations exposed to the sand is an observation more than a century old. There appears to be a synergism between silica and Mycobacterium tuberculosis. The bacteria reproduce more rapidly in the presence of silica, and strains not normally virulent, e.g., Mycoplasma incognitos and M. avium, lead to progressive and often fatal Landouzy-type tuberculosis in a population sharing the same gene pool. The example was the prevalence of tuberculosis in the low land of the Carpathian basin, where silicotic lung conditions were prevalent until the turn of the 19th century and diminished by urbanization.

Oxidant levels, such as those of intracellular peroxidase, are increased by the ingested silica. Also, the silicic acid may act as a stimulus that activates nuclear factor rcB (NF-KB), a pivotal transcription factor in chronic inflammatory disease. The NF-KB factor was first identified as a regulator of the expression of the rc light chain gene in marine B lymphocytes, but it has subsequently been found in many different cells as well. NF-KB is a ubiquitous transcription factor of particular importance in immune and inflammatory responses.101-0 There are gene-specific factors that regulate the transcription of target genes by binding to specific recognition elements. These are located in the upstream (5') promoter region of the gene. 103 The proteins regulated by NF-KB are as follows: proinflammatory cytokines, chemokines, inflammatory enzymes, adhesion molecules, and receptors such as interleukin-2 receptor (gamma chain) or T-cell receptor (beta chain). The activated NF-(kappa)B transcription factor may be a major modifier disguise suggesting signs of CW agent intoxication at a low-density exposure. Mustard nitrogen, as an antimitotic, alkylating agent, found its way from the armor of Mars to the healing means of Asclepius.14,105 Its actions were, and still are, being researched extensively in cancer therapy. 106 The example, which can be applied to Al Eskan disease with a CW agent adjuvant, is the observation that individuals who lack CIPI/WAFl genes can exhibit preferential sensitivity to mustard nitrogen. 107 In contrast, the acute effects of sarin, which is now a weapon of choice for terrorist actions, are primarily the result of unrestricted cholinergic activity at both muscarinic and nicotinic receptors.108-113 Organophosphorus compounds are potent cholinesterase inhibitors, which accounts for their use as insecticides and CW agents. Davies and colleagues report that each year there are approximately 3 million pesticide poisonings worldwide, resulting in 220,000 deaths. In 1990, 1.36 million kg of chlorpyrifos, 4.67 million kg of diazinon, and 1.23 million kg of ethyl parathion were manufactured in the United States,114 paving the way from strictly agricultural use to our nightmare in the future. Loewenstein-Lichtenstein and collaborators claimed that individuals with hypobutyrylcholinesterase serum concentrations or with atypical butyrylcholinesterase levels after exposure to organophosphate agents experience delayed neuromuscular impairments. Follow-up research could not verify this observation. The search for particular gene sequences that may correlate with this aberrant sensitivity remains a promising field in the future.115

We recommend use of the term dirty sand for a subcategory of the dirty dust/dusty CW agents. This term would alert one that the particle is not inert but bioactive by nature and that the formation of dirty sand is not exclusively as a premeditated, planned, and manufactured solid CW agent uniquely but can also be the result of a secondary effect from fallout when dealing with gaseous or liquid CW compounds. The existence of dirty sand may explain why the U.S. CW detectors, sensitive to vapor, did not signal the presence of CW agents in an unequivocally convincing manner. However, the skepticism about the validity of recorded CW alarms needs to be reviewed very critically. As a case in point, Provic estimated 14,000 alarms going off three times per day at least.' From the first to the last day of the air-ground phase of the war, four to five times or more per day, military police patrols announced by loudspeakers MOPP (Mission-Oriented Protective Posture) level 2, 3, or 4 in Al Eskan village, near Riyadh. The US-ARCENT and the living quarters of Lieutenant General Yeosock, the U.S. Army component commander, and his staff, an Army Medical Group command, two Army hospitals above corps level, an air ambulance battalion, and other service and service support units were there to be targeted, fitting into Iraqi BCW war-fighting doctrine. However, the Czechoslovakian Independent Chemical Defense Battalion contingent equipped with Warsaw Pact detectors, and sensitive for solid material, warned creditably of the presence of sarin and mustard nitrogen.

Hazards of the dirty sand remain unaccounted for. The saturated particles, being less than 1 am, would penetrate the troops' protective suits. The protective suit (MOPP) mesh grids and the active charcoal inner-liner poles are significantly larger than the free-floating, CW-saturated sand particles. The MOPP lifetime was originally set for 15 days after breaking the package seals, was then extended for 30 days, and then was extended indefinitely because of the difficulties of resupply and the uncertainties of a realistic lifetime.116 The dirty sand could penetrate the breathable MOPP suits used by U.S. and other NATO forces but would be stopped by the rubber suits issued to Soviet troops and their Warsaw Pact allies. The MOPP suits are designed to allow passage of air and moisture to reduce the possibility that the wearer will overheat. Chemical agents are filtered out by activated charcoal sandwiched between the fabric. However, small dust particles slipped through the charcoal and became trapped inside the suit. The penetration by dusty agents greatly increased with even minor increases in wind speed. The DIA reported test results in October 1990 that confirmed that dusty agents can penetrate MOPP overgarments. Although NATO began issuing permeable suits in the late 1960s, Soviet troops and their Warsaw Pact allies continued to wear impermeable rubber suits, despite the overheating problem. Within days of Iraq's invasion of Kuwait in August 1990, the Pentagon formed a special team that frantically searched for ways to improve troop protection against dusty CW agents. The Dusty Agent Action Working Group quickly came to a solution. A special rubber poncho with a checkerboard camouflage design was issued in limited quantities to wear over the MOPP suit to block the dirty sand.18 The Joint Services Coordination Committee (formed on August 13, 1990) controlled the issue of available stocks of protective, detection, and medical equipment to make decisions about the relocation of stocks within the KTO and to identify requirements for procurement. Medical services were supposed to receive collective protection systems: the XM-28 for corps hospitals and hospitals above the corps level, and the Chem-Bio protected shelters for division-level medical treatment facilities. One of the authors, Colonel Korenyi-Both, the commander of the 316th Station Hospital, U.S. Army, at that time, has no recollection of receiving or notification of receiving protection equipment by any of the subordinate medical units of the 244th Medical Group in its area of responsibilities.

The protective masks' filter was another concern. Because the Army and Air Force were to switch to the M 40/M 42/M 43 series masks in 1988, filter production for the M 17 field mask, the M 25A1 tanker mask, and the M 24 aviator mask had terminated. Filters protecting against CW agents were different from filters for BW agents; both were unavailable for replacement.117 The frequent sand storms, "shamal," quickly clogged the filters, rendering the masks useless. A 26 to 40% failure rate has been reported. 11-120 Only a very limited number of large collective protection system filters were available at the theater of operation, rendering hundreds of Abrams tank crews, and the rear service and service support areas because of lack of shelter, vulnerable to CW agent. To enhance vulnerability with an eye to CW agents, before the war Iraq conducted a search to render the protective masks ineffective by gas mask penetration chemicals. A type of hydrogen cyanide ferric ferrocyanide or one of its modifications has the underhanded effect of dissolving the seals on gas masks and MOPP gear.

The M-12A1 decontamination apparatus and the M-17 lightweight decontamination system, designed for the European theater, were inadequate for desert operations. 121 The fine Arabian sand clogged and rendered ineffective equipment, protective garments, and immune systems without prejudice.

Exposures to low-intensity CW agents have been studied in primates exposed repeatedly to sublethal doses of soman. The U.S. Air Force's Armstrong Laboratory observed a constant lack of detection with CW agent defensive drugs, pyridostigmine bromide in this case, that are effective at protecting against lethal levels of exposure. 122 The Stockholm-based International Peace Research Institute published a thorough study on chronic lowdensity exposure to CW agents but failed to highlight the modifying properties of corpuscula saturated with CW agents.123 Eddington, in his book, records that soil samples were taken from the alleged CW production and storage sites and cites examples from when a Swiss laboratory performed this type of analysis in 1980 on Iranian soil samples. This was also the case in the United Kingdom from the Porton Down facility, using soil samples from Halabja, Iran, after an Iraqi CW attack.8 The German government contributed a total of 60 Fuchs (FOX) vehicles to the U.S. forces, in addition to the two previously purchased by the United States. These were air-conditioned and air-filtered vehicles containing sensors and detectors, providing U.S. forces with their first real-time chemical reconnaissance capability. One of them was tested far CW agent-saturated sand at Aberdeen Proving Ground, Maryland. The British received another 11 of these vehicles, the Israelis 8, and the Turks 4.121 During the breaching operation on February 24,1991, and again on the evening of February 25, 1991, near Ahmed Al Jabar (KTO) airfield, CW agents were detected by the 7th Marine Regiment's FOX vehicles. 124 Recently, on the recommendation of the U.S. General Accounting Office, OSAGWI changed its conclusion about the likelihood of CW agent exposure in the Marine minefield breaching case from "unlikely" to "indeterminate."12 Manley"18 confirmed in his report that the 2nd Marine Division FOX teams collected ground samples and passed them through the proper chain of custody to the Joint Electronic Warfare Joint Captured Material Exploration Center, the U.S. Army Chemical Research Development and Engineering Center, and the Naval Laboratory in al Jubayl; these samples were sent subsequently to the United States for verification of the presence of CW agents. Our efforts to obtain the results have been unsuccessful.

Speculations on the Arab world's "mystery disease" and its relationship to the Persian Gulf War illnesses inevitably would lead our logic to the question of whether the cause of the curse of Tutankhamen was sand-triggered immunodepletion, AI Eskan disease phase I, manifested as localized expressions of multisystem disorder, AI Eskan disease phase II. And the "mystery disease" of Laurence of Arabia, thought to be tuberculosis and probably caused by a rare variant Mycoplasma incognitos as a novel manifestation of old disease, also might have been Al Eskan disease phase II. To broaden our knowledge about this newly (?) discovered medical entity, Al Eskan disease, a thorough historical search is tempting.125-127

Conclusions

In this study we concluded the following.

(1) The physicochemical peculiarities of the sand particles of the central and eastern region of the Arabian peninsula suggest a significantly high percentage (18%) of free-floating sand particles, the aggregate surface area of particles per liter of aerosol, by their physical characteristics, could act as an intensifying factor on low-density CW agent exposure among Persian Gulf War veterans.

(2) Because dirty sand appears similar to dust or fume (fine sand), it shares some of the same characteristics, such as being able to be blown by the wind to any location.

(3) When the CW agent is in low density but absorbed by bioactive particles (sand) in submicronic size, the result easily can be misinterpreted as a non-CW agent ailment that could manifest in a variety of clinical symptoms.

(4) Resulting from the bioactive properties of the Arabian fine sand on the immune system, a toxic synergism was, in effect, eventuated in Al Eskan disease.

(5) When the CW agent is microimpregnated into small, solid particles of silica, its properties may change in the following ways: there is not as much vapor, rendering it less detectable to many vapor samplers (e.g., M8A1 and M256A1 kits and XM93 NBC reconnaissance vehicles); and the agent is no longer a vapor or liquid and thus may not be recognized or noticed. We have no sufficiently convincing data about the FOX NBC reconnaissance vehicle's ability to detect CW-saturated sand.

Based on these conclusions, our ongoing research efforts to investigate the health impact of CW agent exposure among Persian Gulf War veterans are the following.

(1) Systematic time-capsulated sand sample studies to detect CW agent contamination from areas under suspicion of being saturated by CW agents from the theater of operation/Persian Gulf War.

(2) In addition to the evidence presented here of the presence of CW agents in the KTO, the means of sand saturation, and the production of dirty sand, and to further support the general thrust of this paper, we hope to detect CW agent breakdown by-products in the collected sand samples.

(3) Test the presence of antibodies against CW agent breakdown by-products, most likely the more persistent H agents, by monoclonal clone techniques, for example, in the systems of the victims of Al Eskan disease.

(4) Study the neuromuscular junction in muscle biopsies of symptomatic Persian Gulf War veterans by histochemical, electron microscopic, and cytochemical means for detection of the pathomorphology of low-density exposure to cholinesterase-inhibiting chemicals.

(5) Reproduce the role of the sand in low-intensity CW agent exposure among Persian Gulf War veterans in experimental models.

Acknowledgments

The authors thank the following people for their assistance in various stages of this work: Mr. Paul Sullivan, Executive Director, National Gulf War Resource Center; Mr. Anthony Picou, and his wife, SFC (Ret.) Carol Picou; Mr. Robert J. Jones; SGTs Damion A. Deter, Sr., and James H. Young (members of the 2-107th Cavalry); and many more veterans, who chose to remain anonymous, for their moral support, including donation of valued sand samples from the Arabian peninsula. A special thanks is extended to Dr. Erik Schmidt, Mr. Patrick G. Eddington, a former CIA analyst, and MAD John C. Harris, Deputy Chief of Staff, Ohio Army National Guard, for their critical views, encouragement, and correction efforts.

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Guarantor: COL Andras L. Korenyi-Both, MC USARNG

Contributors: COL Andras L. Korenyi-Both, MC USARNG*; MG I,Laszlo Sved, MC HHDF^; Gyorgy E. Korenyi-Both, BSME^^; MAJ David J. Juncer, JA USA (Ret.)sec; Andras L. Korenyi-Both, BSPHYS||; Akos Szekely, PhD(para)

*Flight Surgeon, 2nd Squadron, 107th Cavalry, OI-HARNG, Army National Guard of the United States.

^The Surgeon General, Hungarian Home Defense Forces, Hungary.

^^Drexel University, Technical Operations, Coating Group Coordinator, Stanley Electric U.S. Co., Inc., Philadelphia, PA.

sec Retired Judge Advocate, U.S. Army.

||Surface Science Branch, National Aeronautics and Space Administration, Lewis Research Center, Cleveland, OH.

(para)Professor of Biochemistry and Food Technology, Faculty of Chemical Engineering, Technical University of Budapest, Hungary.

The views, opinions, and findings in this report are those of the authors and should not be construed as official Department of Defense, Department of the Army, National Aeronautics and Space Administration, U.S. Government, or Hungarian Home Defense Forces positions, policies, or decisions.

This work was not supported by a grant from any agency or pharmaceutical company.

Partially presented at the National Gulf War Resource Center's Third Annual Gulf War Veterans' Illnesses Conference, Arlington, VA, September 18-21, 1998, and at the Conference on the Health Impact of Chemical Exposures during the Gulf War: A Research Planning Conference, Atlanta, GA, February 28 to March 2, 1999, which was sponsored by the Centers for Disease Control and Prevention, the Office of Public Health and Science (Department of Health and Human Services), the National Institutes of Health, and the Agency for Toxic Substances and Disease Registry.

Reprint requests: COL A.L. Korenyi-Both, 202 Wickford Road, Havertown, PA 19083.

This manuscript was received for review in May 1999. The revised manuscript was accepted for publication in September 1999.

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