A concept paper on modern explosives, metal pollution, and birth defects.
Hans Husum, surgeon with doctorate in war surgery. firstname.lastname@example.org
Paola Manduca, professor in genetics, Genova University. email@example.com
The precent synopsis is written on request from Professor Terje Einarsen at the University of Bergen. Having read our chronicle in the Norwegian daily Klassekampen on December 1st, 2023, addressing epigenetic damage to unborn life from bomb metal pollution, Terje asked us on behalf of ICJ-Norway and Defend International Law to write up a synopsis of our research and present a professional understanding of the actual problem. Background For 30 years Manduca and her team at Genova University have studied and published extensively on epigenetic effects of micro-environmental agents on cell and organ differentiation. For 40 years Husum has done war surgery with public hospitals and popular movements in the Middle East and Afghanistan and published his research on prehospital trauma systems in peer reviewed medical journals. In 2005 he was invited to Nangarhar Public Hospital in Jalalabad, Afghanistan by local colleagues to examine series of newborn with structural malformations, according to senior doctors of a kind and prevalence never seen before in that province. At this time Husum also got anecdotal evidence from colleagues in Basrah, Iraq of steadily increasing prevalences of abortions, preterm deliveries, and structural birth defects in the provinces in Southern Iraq affected by Western military attacks. However, the circumstances on the ground in Iraq after the 2003-invasion did not allow for scientific studies of the problem. Central Serbia was heavily bombed by modern thermobaric high explosives during the NATO offensive in 1999; Husum contacted Serbian 2 colleagues in Belgrade who reported a significant increase in birth malformations observed from one year after the bombing campaign was conducted. Dahia, the Shia populated suburb in South Beirut, took a high load of Israeli bombardment during the 2006 Lebanon war. Consultations with colleagues at Al Rassoul Hospital, which acts as maternity center for Dahia, revealed the same pattern of birth defects among their patients. Reliable, yet anecdotal, evidence from several war theatres thus indicated a scary epidemiological pattern, which the authors found it mandatory to address for ethical reasons. After the Gulf War on Iraq in 1990, local health workers and humanitarian agencies in target areas claimed that radioactive damage from uranium could be a reason for negative health effect observed in the post-war-period, rightly claiming that depleted uranium was extensively used in metal alloys to improve modern projectiles’ penetration. However, to the best of our professional understanding, the alfa-radiation from depleted uranium is far from strong enough to produce radioactive damage to DNA, thus causing the dramatic increase in major structural birth defects reported observationally. But modern weaponry on explosion spreads multiple heavy metals and metal alloys, not just uranium. In the 1990-ies our understanding of epigenetics became deeper, this new branch of medical science studying how DNA signals are transmitted and cells are communicating. Several solid experimental studies were published documenting that heavy metals and metal cocktails, even in nano-concentrations, could cause epigenetic cellular havoc. Hence, our hypothesis for studies of the epidemiology of the observed post-war birth defects, was that heavy metal pollution from modern high explosives might be a cause of damage to the human fetus by causing epigenetic damage. I.e., that metals can affect the enzymatic and structural proteins and the signaling mechanisms that determine the developmental fate of the cells and the sound structure of organs (see Epigenetics below). It is well established that such interference in early stages of fetal development can cause structural birth defects. Gaza Gaza has since 2006 experienced repeated severe military attacks leaving remnants of heavy metals in the environment. Retrospective studies at Al Shifa hospital showed a progressive increase in birth defects since the 2006 attacks. In 2011 we started surveillance of deliveries alongside analysis of the heavy metals load carried 3 by pregnant women and their babies. Detailed protocols were used for birth registration, and to document the extent of exposures to military attacks as well as other potential risk factors. The data base comprised of three data sets, from 2011, 2016 and from 2018-2019 with 4000-6000 women in each study population. The data demonstrated a significant rise in the prevalence of structural birth defects and preterm deliveries (deliveries between week 27 and 37) between 2011 and 2016, an increase from 1.1 to 1.8% and from 1.1 to 7.9% respectively. Negative outcomes at birth in 2011 and up to 2017 were associated with mothers’ exposure to the bombing in 2009 and in 2014. Study of the extended family and progressed progeny indicated that rise in the prevalence and pattern of birth defects could not be attributed to consanguinity. By ICP/MS analysis we determined the content of 23 metals in mothers’ and/or newborns’ hair. Metal loads since 2014 were consistently high until 2018-2019 for mercury, barium, arsenic, cobalt, cadmium, chrome, vanadium and uranium, pointing to these metals as potential inducers for the increased prevalence of negative health outcomes at birth since 2011. Bodily accumulation of metals whilst residing in bombed areas predisposed for negative birth outcomes. Our data indicate that high loads of mercury in mothers and newborn is consistently found associated with birth defect and high loads of barium with preterm birth. Also the other metals detected by the ICP/MS analysis may cause epigenetic disturbances (1, 2, 3, 4, 5). We do well to notice that the figures here reported from Gaza are based on evident and visible structural defects at the time of birth such as major defects of the rain, nervous system, sensory organs, and the muscle-skeletal system; the prevalences do not include defects or diseases that reveal themselves only later in life, such as anomalies is the heart, hormone system or immune system. Anecdotal data from Gaza indicates that 1.1% of all baby survivors carry defects to the heart, and 0.5% have metabolic faults (personal communication from medical specialists at Al-Shifa, PM). The corresponds well with studies of cohorts of children with congenital malformations from post-war Iraq and Yemen, reporting that 25-30% of the children have defects in the heart and major blood vessels, and 25% have defects in the sexual organs (6, 7, 8, 9). In Gaza we studied toddlers up to 18 months old and found that discrete – yet disabling – damage to emotional and cognitive function is 4 also associated with metal exposure, in case, chromium and uranium. Such malfunction is hard to diagnose in babies, the future may reveal that the real incidence is much higher (10). Therefore, we cannot give exact estimates of the real prevalence of war-related fetal damage in Gaza, but we know that the rates are high, and they are increasing. Epigenetic damage from metals “Endocrine disrupting chemicals (EDC) represent a broad class of exogenic substances that cause adverse effects in the endocrine system by interfering with hormone action. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disrupting chemicals (EDC) have effects on male and female reproduction, cancer, endocrinology of the nerve system, and cardiovascular function.” (11) This statement from 2009 demonstrates that the scientific understanding of epigenetics is a relatively new one. Briefly explained: Cell differentiation, development and extinction is controlled by the gene codes contained in the DNA chromosome in each cell, and new cells are designed from the DNA recipe in mother cells There are two ways to damage this process of life: Either genetically; damage the code. Or by epigenetics, mess up cell performance or the communication between cells – because cells are constantly talking together. For a cell there is many points along the correct “pathway to its proper destination”. The transmission of signals between and inside a cell can be affected in a variety of ways by small interfering molecules such as the heavy metals. Metals can change the methylation status of the DNA, the switch-off function for certain DNA segments, thus affecting the whole function of the cell. Or metals may interfere with enzymatic and structural proteins regulating the cell machinery. Or disturb the communication between cells: Signals are passed between cells through pathways regulated by hormones: the estrogen route is important. Micro-concentrations of certain metals may alter the cells’ estrogen receptors, disturbing or obstructing vital signals, why we call them hormone mimickers or metallo-estrogens. At the stage of primary tissue differentiation, when we consist of just a few hundred stem cells, in our first weeks in the womb, when our organs are under design – we are extremely sensitive to any information coming from the microenvironment; one single failure can be amplified and make the catastrophe. All metals we found in increased amounts in the Gaza’s mothers and babies may have epigenetic effect. E.g., cadmium induces changes to 5 the DNA by epigenetics rather than alteration to DNA sequence. Arsenic readily crosses the blood-brain barrier; hence the brain is easily affected. Epigenetic methylation reactions induced by arsenic are well documented. (12, 13, 14, 15). Other metals with documented epigenetic effect are aluminum, chromium, cobalt, copper, lead, mercury, nickel, selenite, tin and vanadium (16). Three matters are crucial in order to comprehend the potential hazardous effects of metallo-estrogens: One, the fetus is not protected by the placental barrier. These substances pass from the mother’s blood stream, across the barrier into the fetal blood circulation. During pregnancy the mother shares her own load of these metals with the baby. Second, the metals with epigenetic capacity are active in minimal doses. There is no linear progressive dose-response curve for the effect. Several studies indicate that certain metallo-estrogens are more active the lower is the concentration (17). Third, the simultaneous effect of several different metalloestrogens is unknown and thus unpredictable; they may have additive or potentiating effect, we do not know yet. Where are the risky metals coming from? “The new and improved Multipurpose F3 version gives better penetration, fragment pattern, accuracy and improved safety and has enhanced penetration capability. More than 15 user countries in different applications. Combat proven.” Such reads the advertising from the Norwegian state-owned producer of the celebrated 12.7 sniper ammunition. Evidently, local wars are important laboratories for testing of “improved” explosives. Thermobaric weapons are the main source of military pollution of rare heavy metals in Gaza. Through twenty years Gaza has experienced the effects of generations of thermobaric weapons (fuel-air explosives), from the renowned Hellfire rocket to the latest US versions of bunker-busting projectiles. These weapons act by initially spreading a cloud of high-explosive dust which is then ignited to form a sustained massive pressure wave of high temperatures. The cloud of explosive dust flows around objects and into structures before blastoff. The explosive is made of powdered metals, most often aluminum due to the high combustion temperature of this metal. The aluminum particles are coated with magnesium, nickel or other metal alloys (18) The latest generation of thermobaric weapons use nanofuel as explosive, metal particle size less than 100 mμ 6 (nanometers). The nano-fuel based explosives increase the blast pressure by a factor of five compared to previous thermobaric weapons (19) Another source of heavy metal pollution in Gaza is Dense Inert Metal Explosives (DIME). In DIME projectiles the high explosive contained inside the carbon casing is mixed with a powder of heavy metal particles such as tungsten, cobalt or nickel. On explosion, the metal particles yield momentum to the pressure wave, thereby massively rising the energy of the blast. DIME weapons were used by Israel in the 2006 Lebanon war (personal experience by author, HH) and repeatedly during attacks on Gaza. Tissue samples from war wounds in Gaza in 2006 contained very high concentrations of carbon plus traces of unusual metals such as copper, aluminum and tungsten, a revealing fingerprint of DIME (20, 21). The epigenetic effects of tungsten-alloys have long been well known. Low-dose environmental pollution of this metal increases the risk of cancer diseases, especially is leukemia in children documented (22, 23). What kind of future are we looking into? The pollution of heavy metals in the target areas is permanent. Our studies in Gaza documents that the metal concentration in mothers’ hair remains over years (4). The metal dust and nanoparticles from explosions and demolished structures spreads everywhere and enter the tissues of humans and animals by inhalation, contact, food and water. Heavy metals are not eliminable from the environment. Preventive measures are inconceivable, and so are clean-up operations. Thus is generated a chronic high level of human contamination that cause not only more and more birth defects ,but also of other non-communicable diseases, as cancer, diabetes, and male infertility – all observed to have risen in the specific context of Gaza. I The long-term effects of heavy metal pollution should concern us because the epigenetic imprints may be trans-generational, carried on to grandchildren’s children and further when metallo-estrogens affects the germ cells of the fetus. The sexual organs are shaped during the early blast stage when the fetus is 7-8 weeks old. At this stage the germ cells are very sensitive to programming failures. However, damages in the germ line may not be evident at birth; they manifest themselves later in life and can be transmitted to coming generations (24, 25, 26). 7 Discussion The ecology of environmental pollution and its effects on human physiology is complex. What is scientifically documented from Gaza is the following: 1. Heavy metals weapon components are detected in wounds of war victims. 2. There is a correlation between documented exposure to military attacks and increase in prevalence of congenital defects and in preterm births. 3. The adverse effects are associated with highest load of heavy metal contamination of women and newborn in the population. 4. High loads of several specific metals were associated with adverse effects both in 2011 and 2016: Birth defects and mercury loads in the hair of newborns; preterm births and barium concentrations. 5. The heavy metal contamination ensues from documented acute exposure of mothers to attacks and also from chronic exposure to weapon residues. 6. The heavy metals detected in human tissues have epigenetic potential that can explain the epidemiological pattern of preterm deliveries and structural malformations. 7. No other confounding occupational, environmental or nutritional source of heavy metal or has been identified which can explain the epidemiological alterations in preterm deliveries and neonatal malformations. Because linear causality does not exist in complex epidemiological models, we must read patterns. Metals’ epigenetic interference is governed by a stochastic modality, i.e. is not all or none, but a probabilistic event. Therefore, the consequences of metal pollution by weaponry must be evaluated in terms of increased probability of a certain effect. To the best of our understanding the damages to human life indisputably documented in several scenarios of modern warfare cannot happen randomly. There are other risk factors for miscarriages and fetal disorders such as malnutrition, chronic diseases, kinship-carried genetic disorders. However, the consistent pattern of damage to unborn life and the persistence in time observed in the war theatres during the last decades can hardly be explained by other causative mechanisms than environmental resilient metals inducing epigenetic damage (27, 28). 8 Accountability The producers, dealers and users of modern heavy-metal based high explosives – should they have recognized the risk of damage these weapons yield to the fetus? Considering the grimness of the problem, the scientific documentation of the study matter is amazingly inadequate. There are no comprehensive scientific studies, other than in Gaza, giving detailed confirmation of the exposure, of the level of contamination of humans due to exposure, and the effects on reproductive and general health. And there are no studies available, other than in Gaza, investigating the persistence and changes of heavy metal environmental pollution over time, monitoring the associated changes in reproductive and pediatric health. The seemingly lack of scientific interest may be due to discrete restrictions of access to the study matter: In 2013 one of the authors (HH) was invited speaker to an AllIraqi scientific conference on medical emergencies and trauma in Basrah. The audience comprised of professional colleagues, all of them probably aware of the accelerating epidemic of post-war birth defects in their homeland. However, the issue of malformed newborn was not on the agenda. So, the author asked the conference chair – a colleague from Baghdad, vice-minister of health – permission to announce interest in the matter and invite a few colleagues for informal talks. Request denied, “Sorry Doctor Hans, we have some friends, you know”. Having done a study on the prevalence and types of birth defects in Falluhja one of the authors (PM) was intimidated and restricted from publishing the results through pressure on her colleagues In Fallujah, and there the malformed child survivors are locked up in a special “rehabilitation center” protected by a private security company; only mothers and fathers have access (29). Nonetheless observational data and scientific strong warning signs of the unfolding tragedy have been readily available for twenty years (ref. 1-17). However, the red lights have been ignored: We have studied patent request from weapon producers in the US. The recipe for new types of nano-fueled explosives based on a wide range of heavy metals is given in detail in the applications, also the expected enhancement of the military potential, and the benefit for the producer’s country. But not a single word is written on potential adverse effects of the metal cocktails on the nature world and on humans, and precautions are absent in these requests. 9 Conveniently, the hidden dead and damaged newborn are voiceless and are in numbers that are sometimes – if not always – higher than those directly killed or maimed by the weapons. This must change: Scientific evidence is still imperfect. However, we do know enough at the present stage to get metal polluting weapons banned. Somebody has to stop the ongoing chemical war on unborn life.
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