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Your Environment. Your Health.

Visionary Ideas: Biological Mechanisms

New Strategic Plan

Visionary Ideas

NIEHS established a special website for visitors to submit, vote on, or comment on Visionary Ideas, as well as discuss strengths, weaknesses, opportunities, and threats for NIEHS. Visionary Ideas are as submitted, unedited for grammar or spelling.

Idea 1: Autism and high interest pathways

NIEHS should do a scan of the literature and map all the pathways affected by autism in the literature so far. Determine where most of the findings in the literature converge thus providing a list of target pathways for intervention. A simple comparison of NIEHS’s vast database can provide a list of chemicals, toxins and pollutants that affect those pathways. Not only will this help provide direction of environmental research by giving us priorities in the 80,000 plus chemicals out there but we will also determine the most affected pathways in autism. Research like this will help all affected autoimmune and neurodevelopmental disorder susceptibility groups by honing in on uses of household chemicals of interest, particular pesticides, etc., that we know affect critical pathways and will provide environmental clues for follow up that ordinarily we might miss.

 

Comment

All carpeting and other floor coverings should be checked for chemicals that are used in their manufacturing that may be affecting the occurrence of autism in children after 18 months. Vaccines are often blamed but it should be considered how much time infants, toddlers and older children spend crawling, playing, sitting on these floor coverings as well as playing and chewing on or licking toys or other articles that have been on the floor

Idea 2: Autism and the microbiome

Research shows that individuals with autism have microbiomes that are different than siblings and age/sex matched controls both in numbers and types of good and bad bacteria. NIEHS should determine how disturbances in gut microbiota are affecting autistic individuals and if replenishing the microbiome can be an effective treatment for autism’s comorbid immune and gastrointestinal conditions.

 

Comment
The possible role of probiotic therapy in children with autism is important to research. Many parents have found their children improved when given probiotic dietary supplements. The role of antibiotics (which diminish the gut flora) should also be researched, particularly in relation to the timing of live virus vaccinations such as MMR and the new hexavalent child vaccines.

Idea 3: Autism and toxic body burden

Compare the toxic body burdens of individuals with autism vs. age/sex matched controls. Determine biomarkers of interest based on toxic profiles of autistic individuals. For example, we might have lymphocytes from autism and unaffected controls and test for biomarkers of mitochondrial function or immune stimulation from the various chemicals and at various doses.

Idea 4: Chemical-biological agent interactions in environmental disease

Chemical/bacterial or viral interactions likely contribute to many chronic diseases, including cancer and cardiovascular disease. The DNA and other macromolecular damage imparted by chemical agents can be embellished by underlying bacterial and viral infections that can recruit the immune system leading to inflammatory responses. For example, the tumor microenvironment is propelled by the recruitment of a number of different cells in the immune system and superimposition of DNA damage can forward disease processes. Both experimental models and human studies are needed to tease out these interactions. Such knowledge can lead to the design of intervention and prevention strategies.


Comment 1

There appears to be a coalescence of Visionary Ideas entries related to this topic, with a central theme of interplay between environmental exposures, individual susceptibility, and underlying or ongoing infection, inflammation and immune deregulation. This seems like an important and recurring theme for the Strategic Plan.


Comment 2

I love this Idea

 

Fibromyalgia or “Chronic Fatigue Syndrome” most always is associated with a Specific Trauma. Many Viruses come out of Hibernation with Trauma. The 1st. Anti Viral Drug (Acyclovir) was 1964. The theory behind Viruses is to put them back into Hibernation.

 

Therefore when your Environment is Toxic that would act as a Stressor to bring a Virus out of Hibernation. So in order to put the Virus back into Hibernation you would want to Eliminate most of the Stressors that brought the Virus out of Hibernation like—Mold---Toxic Thought Pattern---Air Quality---Water Contamination---Bad Marriage---Radon---Chemicals---Etc.


Comment 3

This is an enigmatic category for me since one usually associates NIEHS with chemicals in the environment. However, many biological concerns are becoming appreciated and are not fitting squarely in any agency's bailiwick.

 

For example, prion migration through endogenous animal populations, who really studies how that happens? There has been speculation about hunting and gut piles. Of course, animals die naturally and are consumed by a wide range of creatures. It may be really important to know how this works. Will prion disease become endemic? How many species can it eventually jump?

 

Tick born diseases are prevalent around the world, but what one finds available in the way of information is either a medical discussion of diagnosis and treatment or an epidemiology of disease study. Who looks at how ticks survive and spread in the environment, especially our unique densely occupied human environments as opposed to forests, prairies and animal production facilities? Not only is global warming an interesting consideration here, but we have serious questions to answer about the coexistence of human and animal populations, including both wild animals and our pets. The implications for children may be greater than for adults. Here in Cincinnati, many neighborhoods are overwhelmed with deer. People love the animals, but having so many deer in our residential areas comes with a risk of more than chewed on shrubs.

 

Bed bugs are another recently touted health problem. These exposures come in doors and responses to bed bug infestations come with all kinds of concerns over the proper choice and use of pesticides.

 

Our cats are terrible vectors for viral infections, as are rodents. We know that there is a problem with human viruses infiltrating our ground water. Do we know enough about the life cycles of viruses in the environment or are we just assuming they are only transiently there due to human release? The BIOWATCH (homeland security biological agent detection systems) systems distributed all around the country have been picking up hits due to bacteria we never expected to find in cities. Perhaps this shows how little we think about our cities as ecosystems? Certainly cities have many animals, some in big numbers, like cats and dogs, squirrels, birds, etc.

 

Avian flu, west Nile virus, God knows what else, visits our cities through animal populations. This is not the kind of thing one expects the department of agriculture to be looking at since it is not an aspect zoonotic diseases we usually emphasize, unlike the risk of animal worker exposures. How much animal detritus is spread throughout urban areas? I grew up using the subway every day in Boston, ask me about pigeons and train stations!

 

Finally, our old friend the cockroach, and likely other species of insects, and most fur covered animals, are associated with allergies. Roaches in the wild do not cause this. Roaches in our homes, hotels, restaurants and the like are the source of the problem. This is our environment, our urban environment. It seems we don't know too much about this. Perhaps we need a new discipline of "urban ecology". (I'm sure people will jump up and say they ate teaching courses on this already.)


Comment 4

I believe the most practical answer to all these susceptibilities to infection, allergy etc. lies in individual maximization of the immune system. Easier said than done.

 

Pasteur stated that "le microbe n'est rien; le terrain est tout", inferring that if one's health was in good shape, one would be resistant to infections. Ditto with allergies. Unfortunately, this crucial aspect of medicine (preventative) is not prioritized in the US, since really healthy people have little need for drugs, doctors or other forms of health-care.

 

Tackling the proliferation of chemicals in the American environment from all sources (water, air, food and medication etc.) entails a David v. Goliath struggle, since those bodies responsible for contaminating the environment, whether directly or indirectly, have 99% of the power and show little willingness to voluntarily address these issues.

Idea 5: Circadian rhythms, clock genes and environmental stress

In the last 10 years we have learned that virtually all cells in the body have a molecular clock and circadian patterns of physiology and biochemistry.

 

Studies have shown that the clock is an anticipatory clock and that it prepares the cell for the stresses in the environment. In addition, research has shown that when the internal cell/tissue clock is not in sync with the environment (e.g. lighting) that pathologies in many different organ systems occur.

 

For the NIEHS, incorporating chronobiology in our understanding of the etiology of disease associated with environmental exposure or living conditions is critical. Two examples of areas of study include:

  1. Time of day effects of toxin exposure, are there times at which the cell/tissues handle the exposure better? can we learn strategies from that?
  2. Effects of shift work and associated lifestyle (light cues, feeding) that impact on the synchronization of the systems clocks: links to metabolic disease, cardiovascular disease, cancer and neurological diseases

Idea 6: Develop robust biomarkers

The individual host's response to the environment is highly variable and not always clearly predicted by the amount of exposure. We should develop a set of robust biomarkers to quantify the actual response to the environment. As a simple example, liver transaminases are frequently used to determine if alcohol has any hepatocellular toxicity. The increase in blood level of transaminases shows how much toxicity the alcohol induced.

Idea 7: DNA changes as environmental dosimeter & predictor of disease

Somatic DNA modifications (mutation, copy number variation, methylation, chromatin, etc) accumulate with age and exposure and can be transmitted to daughter cells making a semi-permanent record. NIEHS could lead the effort to describe the tissue-specific accumulation of DNA changes over time, how diet, environmental exposure, lifestyle and genotype modify this accumulation, and whether such genetic and epigenetic modifications can be used as a measure of disease risk.

Comment 1

I think that this is a critically important area of research. Having just come back from chairing the latest IARC monograph, it is clear that such data would be essential in the near future for moving the evaluation of agents to 2A (probable human carcinogen) to 1 (human carcinogen). Developing these methods and figuring out how to apply them in environmental settings to humans may be the most valuable development in molecular epi that could be possible. In addition, application of these and other methods to germline mutation is of the highest importance and in need of development to assure the health of future generations.


Comment 2

this 'idea' crystallizes a concept of high value to both the intramural and extramural communities at NIEHS. Certainly, this institute SHOULD be a leader in understanding the impact of the environment on our genome/epigenome.


Comment 3

I think it is becoming increasingly apparent that genomic functions impact epigenetic processes. The idea that NIEHS lead research efforts using both intramural and extramural resources to focus on how the environment can modify/damage DNA and alter genetic/epigenetic processes is timely and necessary to enhance understanding disease risk.


Comment 4

The idea being raised here is very important: namely to what extent can the genome inform us about our individual time travels through the environment and how can this information be related to environmental health risk.

 

Premise: Technology such as next and way-next gen sequencing will assure the opportunity to sample DNA space (mutations, CNVs, methylation), as well as expression space [possibly just microarrays], across the life of an individual. This could be extended to assessment of the individual responsiveness to environmental stresses.

 

Challenge:

  • A) To relate the vast amount of information that would be collected including the changes in the various endpoints that will be observed (one example being the DNA dosimeter) to environmental factors.
  • B) Discern internal vs external environment at a health related level. For example, inflammation is a prominent stress that can arise from internal and external sources and is a likely inducer of genomic change (such as cancer) in addition to its broad range of disease consequences. (The challenge is obviously much less for cases of high chronic and/or acute exposures single agents like aflatoxin.)
  • C). Integrate genomic changes (at the DNA or the expression level) to meaningful human biological differences including disease susceptibility, which would be a major epidemiological problem.

 

Comment 5

The idea strikes to the core of toxicology goals as applied to genetic material, i.e. understand the impact on the structure and stability of the entire genome, rather than infer possible impact from model studies. It also suggests a biological measure of lifetime exposure (related to several Ideas submitted to this Forum).

 

While now the use of the whole genome as a dosimeter (or reporter) of changes caused by environmental insults appears is not cost effective, it is likely to become efficient in near future - the hope that has been given by exponential decrease in sequencing cost and increase in sequencing power over the last several years. In fact, it may be the right time for NIEHS to lead the genomics toxicology and genome-based dosimetry effort because it can trigger progress in several fundamental and technology areas which may not get the timely momentum otherwise.


Comment 6

To further underscore this visionary idea and develop the idea and infrastructure required, the NIEHS must consider that complex diseases linked to environmental insults, such as asthma, cancer, diabetes, heart disease, etc. are quantitative heritable traits. Environmental exposure related disease are likely heritable and may occur in both the present or future generations (somatic and germ cells) as noted. The size of the effect of multiple genome wide DNA modification has to be understood at the human population level in order to identify the targets that alter homeostasis and lead to disease. The NIEHS is well positioned for molecular biology and genetics but not for population genetics/epigenetics and susceptibility to toxicity and disease. Experimental models must incorporate both genetic and epigenetic diversity in order to identify the polygenic mechanistic basis and predict disease. The NIEHS should support the development of the strategies and tools required for exposure biology and quantitative genetics in order to identify and dissect the function of mutations and epimutations that have the greatest size effects in varying populations structures and exposures.


Comment 7

The idea of determining how our environment effects our genome and using this information to determine exposure and to predict health effects is a grand, exciting idea that should be at the heart of the NIEHS mission. It also is a very challenging one that will require much thought as well as continued advances in sequencing technology and bioinformatics to accomplish such a project in a meaningful, practical manner. But the time is certainly ripe for thinking about how such a project might be accomplished, perhaps through a series of workshops or symposia, and perhaps piloting some aspects of data collection and analysis. NIEHS has many strengths that will be needed for such a project and it would make a natural core for initiating and coordinating this grand challenge, but it also will need the involvement and support of a considerable fraction of the biomedical research community.


Comment 8

I think it is imperative that we understand how DNA damage influences genome stability and decrease quality of life. For this understanding to occur, we need to study on a molecule by molecule basis the distribution of multiple types of damage, whether that damage interferes with the replication process, and what repair, DNA checkpoint, and DNA damage signaling proteins respond to that damage (i.e. they are co-localizing with the damage).


Comment 9

The epigenetic aspect in this visionary idea should be further emphasized.

 

As far as I know, NIEHS has the epigenetic among its priorities. This should continue and further effort should be made for an healthy understanding of the interactions between the environment and the tissue specific epigenetic marks.

 

This understanding should be at least in two-fold: (1) how adverse environmental conditions affect the epigenome and (2) how a given epigenome reacts to the environment. This understanding will help the development of the epigenetic fingerprints as well as specific target loci for a specific environmental factor or group of factors in similar tissue types in the body. This can also help identifying vulnerable population for an environmental factor or group of factors. Collectively this information must be utilized for developing not only diagnostic and therapeutic approaches but also, and perhaps more importantly, preventative measures.


Comment 10

I consider this a top priority goal and am in agreement with essentially everything contributed in comments so far on this issue. We know that our genomes accumulate damage and that different environmental settings result in different exposures. The methods are becoming available for sensitive high-throughput screening of DNA for particular alterations and eventual correlations with disease. The NIEHS should lead the way in this important area.


Comment 11

I think that the research in this area is fundamental to reveal the interactions between environmental and genetic factors. It should be a top priority of NIEHS. The research in the area will be highly rewarding but challenging, requiring close collaboration of many scientists including biostatistician and bioinformaticians.

Idea 8: Environmental exposures and stress

NIEHS should more research on the relationship between exposure to environmental agents and stress particularly living in riskscapes may lead to higher levels of stress (allostatic load) that can lead to poor mental health outcomes, hypertension, CVD, diabetes, stroke, autoimmune diseases, and other negative health outcomes.

Comment

Environmental exposures are STRESSORS. Environmental health outcomes are mediated by a wide range of stressors (including those that are biological, chemical, physical [and what is commonly called "stress"]).

Idea 9: Environmental factors in inflammation and associated diseases

Currently, it remains unclear how environmental factors (for example, exposure to estrogen-like compounds, cigarette smoke etc) regulate the immune system and inflammation. An improved understanding of the interactions between the environmental factors and immune system is likely to identify new approaches to treat diseases that are associated with inflammation (for example, certain cancers and autoimmune diseases).

Comment 1

I agree. I would like to add to the list of environmental factors to be studied, nonionizing radiation of the sort from cell towers, wireless devices (including smart phones, wireless keyboards, Wi-Fi, etc..).

 

As someone who is sensitive to emf in the microwave and radiofrequency range, I would be particularly interested to learn more about how EMF affects inflammation and the immune response.


Comment 2

i agree i am a cancer survivor of 16 yrs. it is so important that we have prevention on all aspects as to how to protect the community as well as learn about the effects of the environment and what we can do to better inform and protect ourselves and most important how do we reduce the numbers of cancer and protect our children who are exposed to second hand smoke and environmental issues.


Comment 3

Inflammation plays a critical role in our everyday life. As an example, how many of you have taken an anti-inflammatory drug (aspirin, ibuprofen, acetaminophen, etc.) in the past month? Many people try to control their inflammatory response. NIEHS should attempt to understand the basic mechanisms of how the environment modifies inflammation, to improve public health.


Comment 4

There are many health problems which begin for no reasons that we know about. If we can identify what in the environment is causing these problems, then we may be able to prevent the problems. Hormones and antibiotics in food, drugs and chemicals in drinking water, and other changes to the environment may explain why some health problems are happening more often now than they did before. It could help people to be healthier, and possibly save a lot of money, to figure out what causes the problems. Inflammation is a reasonable place to begin.


Comment 5

There would be a greater need to have an integrative environmental genomics approach to better understand the environmental contribution to health outcomes given the fixed genetic and dynamic epigenetic factors within and between individuals.


Comment 6

Very Well Put.

 

We need to study the Environment of an Individual Person and Determine what were the Factors that Caused the Cancers or Illness. I like your approach.

 

The Navaho Medicine Man used to Treat not only the Patient—He also Treated the Community. The Medicine Man felt the Community also played a Role in the Illness. Part of the Solutions or Medicines to the possible Treatment of Cancers could be the Subset or the Causes to the Cancer.

 

Example --------------

The patient lives by a Toxic Rubbish Dump. The Patient lives next to “3 Mile Island. The Patient eats 20% of their Diet in Trans fats. The Patient eats 40% of the Diet in Fast Foods. The Patient has Repetitive Negative Thoughts and Wants to End their Life. The Patient has given up their Hope and Vision. The Patient does No Exercise and takes No Vitamins. The Patient is Bi-Polar and has never been Diagnoses or Treated. The Patient has suffered from Extreme Physical Depression and has never been Treated Medically or Cognitively. The Patient is Borderline Diabetic and has never Regulated their Diet. The Patient has a History of Abusive Relationships.

 

Comment 7

This Strategic Plan idea asks if environmental exposures affect the human immune system. We should also ask the question from another perspective: how does inflammation affect a person’s susceptibility to environmental exposures? The pathophysiology of inflammation starts with tissue damage (e.g., infection, radiation damage, autoimmune disease) that leads to phagocyte infiltration and generation of cytokines and reactive oxygen and nitrogen species. Host epithelial cells are chronically exposed to these biological and chemical stresses. How do these endogenous stressors affect cellular responses to environmental exposures? Epithelial cells exposed to local inflammation may be more or less susceptible to DNA-damaging environmental toxicants (metals, alkylating agents, radiation, etc.) due to up- or down-regulation of DNA repair mechanisms. How does chronic H. pylori infection of the stomach and the resulting gastritis affect a person’s susceptibility to environmental exposures from food-borne toxicants? How does influenza infection of the lungs affect a person’s response to airborne toxicants? Colitis and inflammatory bowel disease are well known to affect liver function via the portal circulation, so one might ask how these forms of chronic inflammation could affect hepatic metabolism and activation/detoxification of drugs and environmental chemicals. Further, IBD can disrupt the epithelial barrier in the gut, which can affect the absorption and toxicokinetics of chemicals in food and water. Chronic inflammation may thus have significant influence on individual susceptibility to environmental exposures.

Idea 10: Environmental triggers of autoimmune disease

A rapidly expanding body of science is showing that the environment we live in has many diverse effects on triggering the onset of disease in humans. Impacts on health go far beyond the conventional notion of “bad” substances in the environment causing disease while “safe” substances do not cause disease. The burgeoning field of epigenetics is demonstrating clearly that even supposedly benign chemicals can turn specific genes on or off. So, DNA is no longer the sole determinant of disease propensity. One must also look at which genes are active to predict a person’s future health.

 

Autoimmune disease research has clearly demonstrated that all types of chemicals and non-chemicals in the environment can trigger the onset of one or more of the genetically inter-related family of autoimmune diseases. Potential triggers include “harmless” chemicals, foods, medicines, and even sunlight in addition to bacteria, viruses, and hazardous chemicals and pollutants. This is why identical twins growing up in the same household have only a 30-50% concordance for autoimmune diseases. If environment were not a major factor in autoimmune disease onset we would expect to see concordances close to 100% since the twins have identical genetic make-up.

 

There is a growing body of scientific and clinical evidence of overlapping etiologies between immunodeficiency disease and autoimmune disease, and cancer and autoimmune disease. For example, skin cancers and certain autoimmune diseases can be triggered by exposure to sunlight. Another example indicative of overlapping disease triggers is the increase in both autoimmune thyroid disease and thyroid cancer after the Chernobyl disaster due to radioactive iodine exposure.

 

Therefore AARDA strongly recommends that NIEHS take a leadership role in studying the full range of potential interactions between diseases (cancers, autoimmune diseases, etc) and the much wider range of environmental triggers than we currently study. In addition to first order interactions, we strongly recommend that NIEHS study synergistic interactions among environmental factors and disease, e.g. while radon and cigarette smoke individually can trigger cancer, exposure to the combination synergistically increases cancer risk. The impact of the recommended research direction will have huge impacts on improving human health as we get a more complete understanding of all the environmental triggers causing onset of many diseases.

 

Comment 1

We must understand these diseases much better; I have heard of three more people in the last week who have been diagnosed with autoimmune disease.

 

Comment 2

We certainly need to know what things in our environment that are triggering autoimmune diseases, which are on the rise!

 

Comment 3

Autoimmune diseases are growing significantly in the past ten years. It has to be an environmental factor as genetic factors do not change that rapidly. The biological mechanisms involved need much more research. The study of toxins is important but how that toxin interacts with the immune system and one's genes is an important next step in research. Also, why are more women than men affected by autoimmune diseases. Could be something in the women's environment that is a contributing factor.

 

Comment 4

After retiring as a guidance counselor, I helped another counselor at another school with state and local testing. We worked out of a closet that had been a janitors closet and storage for science classes. Obviously chemicals had been stored in this closet. After working in this closet for a number of years, my friends was diagnosed with Addison's Disease. After helping her for seven years, I, too, was diagnosed with Addison's Disease. I asked both NADF and my doctor about a connection, but there is no research in this area. So, YES, I think research is needed in this area.

 

Comment 5 

At the Graves’ Disease Foundation, we have connected with literally tens of thousands of patients and family members who have been impacted by this autoimmune disease. An all-too-common refrain that we hear is, “I’ve lost everything due to this disease.” Patients not only find their health compromised, but also their overall quality of life, their ability to complete basic day-to-day tasks, and their ability to make a living to support themselves and their families. With autoimmune diseases being diagnosed at an alarmingly increased rate, our nation cannot afford to ignore this critical area of research!

 

Comment 6

In 1998 I was told that I had Addison's and the next year is was told I had Graves. September of 2010 I went to the E.R. and was told I have Type I diabetes. I have two daughters, when the youngest (now 4) was about 18 months I noticed my speech slurring, my left hand would shake when I held thing that was light weight, and I would stumble, things have gotten much worse. I have had a doctor tell me I look great on paper regarding lab results, I have had Genetic test, lumbar puncher, and MRI's. So far no one knows what is going on. Also no one in my family has Autoimmune disease. Something in the environment could be to blame.

 

Comment 7

It is at the most importance to study "Environmental Triggers of Autoimmune Disease". Autoimmune diseases, like Addison's disease or Schmidt's syndrome are chronic and change person's life forever. This research would benefit many. It would also raise awareness about the environment and how it affects our health.

 

Comment 8

The environment/health interfaces evidenced for this idea are well worth increased attention; in particular, due to the growing body of empirical evidence about the outcomes of environmentally-mediated auto-immune dysfunction.

 

Comment 9

I am an otherwise healthy, active, organic food-eating, home birthing mother of three, and at 42 I was diagnosed with Addison's disease and went through menopause (too old to call it "early", but early nonetheless!). I've never had toxic housecleaning products in my house, never go to dry cleaners, work as a biologist so I'm outside in wild places often...Why did I get an autoimmune disease? How can others prevent it? If there is an environmental trigger, what is it? This study is important for all the growing list of autoimmune patients.

 

Comment 10

I would like to see Nuclear Exposure Added to this List. I believe that many Auto Immune Diseases are linked to Nuclear Exposure. There are many great areas to get statistics like “3 Mile Island” Meltdown, ”Rocketdyne” Meltdown, “Chernobyl” Meltdown and “Japan Meltdown”.

 

Comment 11

Pesticide and herbicide caused "chemical immune system damage" from both short term high level and long term low level exposures and the resulting increases in human sensitivities to the chemicals and resulting adverse medical symptoms must be a primary area of this study. The rationale is the vast number of people who have been exposed to pesticides and herbicides as industry and layman users of pesticide and herbicide industry products and who are, as a consequence of exposure, left permanently incapacitated and/or suffering from the affects of exposure. Those exposed who are negatively affected often have no clue as to what is causing their illness and are often misdiagnosed by a medical industry unacquainted with chemical poisoning leaving the patients untreated for the cause of their unpleasant and life threatening symptoms and without hope of recovery from something beyond their understanding. Consequently and unfortunately, only those who have connected their symptoms with exposure to pesticides and herbicides report it as such. This can mislead us into thinking the problem is much smaller than statistics indicate. Those negatively affected from both short and long term exposures to pesticides and herbicides come from large segments of the population including but not limited to: pesticide / herbicide industry workers, farmers, farm workers, land developers, those who buy new houses, rent apartments, treat their land and property, work in a facility, work in or go to school, and buy exterminator services for their living environment. Many cases of exposure and illnesses can be found on the internet. I also offer my exposure and consequences for those interested in understanding the problem in greater detail.

 

Comment 12

The recommended change in paradigm of looking at autoimmune diseases, cancers and other diseases which have a strong environmental component is critical to NIEHS' ability to maintain its leadership in environmental health research. The current approach of studying chemicals individually is too simplistic. This is exemplified by the large expenditures and long time required to study a single chemical. At the current rate of research, NIEHS will become irrelevant as it gets further and further behind new risk findings. In addition, NIEHS will be missing the opportunity to be a leader in getting an integrated understanding of the many ways in which the environment influences our health, both negatively and positively, especially in combination with chemical, viral and other exposures. The research approach expressed here is absolutely critical to lowering healthcare costs and improving the nation's overall health.

 

Comment 13

Further investigation into environmental triggers for auto-immune disorders is desperately needed. In my family alone six folks have an autoimmune disorder, and my poor 10 year old has two! Whether it be diabetes, alopecia. hypothyroid, or whatever, these diseases significantly impact one's life and cost the healthcare industry and the patient a ton!

 

Comment 14

Multiple family members have 2 or more auto-immune disorders. I'm hopeful for the discovery of environmental causes.

 

Comment 15

Know anything about chlordane? My site was treated prior to it's construction and family members have had interesting illnesses...

 

Comment 16

PLEASE understand that all people are adversely affected by toxic chemicals and radiation. People who have the diagnosis of Chemical Sensitivities/Intolerances, MCS (Multiple Chemical Sensitivities) have been "attacked" by the very manufacturers of the chemicals that make ALL of us sick, eventually. As a typical MCS/Chemically Sensitive person, I have NO doctor to see unless I pay for it, no housing unless I accept a diagnosis of "Mental Illness," and cannot afford to buy so much as the food I would need. I represent more than one million people who would vote on this very webpage if they were able to use a computer. People who have Chemical Sensitivity have lost their ability to breathe or think near phenolic resins in computers! Please, rethink this idea about auto-immune diseases connecting with chemical exposures. People who have Chemical Intolerance need HOUSING, FOOD, TRANSPORTATION, INCOME and all the things that people with auto-immune disease already have. The chemical industry has fought us for over 25 years so that we get absolutely no support from the federal government. I actually voted for the auto-immune idea because it is based in sound science, but people who have chemical sensitivity also suffer from Crone's Disease, Rheumatoid Arthritis, Heart Disease, Thyroid Disease, Cancer and other disorders but they cannot find a doctor, can't go into the doctor's perfumed office, can't find affordable non-toxic (Pesticide-treated) food to eat, and certainly cannot live in a house that has ever been treated with chlordane for termites, or ever sprayed for any kind of insect. As a personal sufferer, I was unable to walk outside my own home due to lawn spraying! I simply laid on my couch for years on oxygen because THERE IS no care for us. Please, at least vote for both of these ideas! SJ

 

Comment 17

Autoimmune diseases are rising significantly. recently type 2 diabetes has been shown to be autoimmune. It is alarming how the number of people with autoimmune disease is increasing. There must be something in our environment that is playing a role. They mostly affect women and so far research has not shown why that is true. There needs to be research into products that women use that are thought to be safe but perhaps interact with one's genes and cause inflammation. It seems like inflammation is a major factor in autoimmune diseases. It is about time the government took these diseases seriously as they are usually not even mentioned as when there is a reference to chronic diseases yet millions of Americans have one or more of them. The health care cost to treat these life long disabling diseases alone should make the congress take notice instead of always protecting their favorite condition.

 

Comment 18

Tanaparry asked about chlordane on April 27, 2011. See CDC article on the Encyclopedia of Earth: http://www.eoearth.org/articles/view/155483/ 

 

Comment 19

I was diagnosed almost 4 years ago with NMO. There is no one in my family history with an autoimmune disease as far back as my relatives can remember. I began having symptoms (migraine headaches, IBS) approximately 14 years ago. I had been working in a window factory spray painting 40 hours per week with no ventilation, etc. for a total of 10 years. At the time my symptoms began I had asked to be transferred to another job because I would experience the headaches in the midst of the spray painting, but instead was told I needed a physician excuse to even use the restroom by my supervisor. I have never investigated the possibility of this causing my NMO, but do feel it could possibly have played a role in my immune system issues. Thankfully I have been away from that workplace for 11 years now, unfortunately I will suffer with NMO for the remainder of my years.

 

Comment 20

My grandson, age 10, is making great strides in recovering with Autism. His parents have completely redone their home to eliminate all man-made materials from it. This is in addition to his strict diet of gluten free and preservative free foods. Certainly our environment affects us in all autoimmune diseases.

 

Comment 21

I currently have Scleroderma, however I have had an autoimmune disorder since 2001, diagnosed & treated since approx. 2003. I so far have a mild form of Scleroderma that has been to this point slow moving, however i take many meds to control. I work in a rural building but I consider to be a sick building as we have mold & poor ventilation, I originally had pneumonia a couple of times & then acquired the undifferentiated connective tissue disorder which settled into Scleroderma & a few other little ones. I started this job in 1999 & feel that the stress level & the building are the reasons I am sick, however I do not have the luxury of quitting to see if they are the issue because the insurance is through my work. Unfortunately the only way I would know if it is the building & the stress would be to quit & not have stress which is impossible. I feel it is the way my body breaks down the stress that contributes to the disease. I am very allergic to mold etc. yet work in dust & mold daily. No win situation I guess, would be nice if someone would determine if any of this is an issue.

 

Comment 22

Autoimmune disease has risen by 400% since the 1950s. What has changed? The environment. We've been exposed to the fallout and radiation of hundreds of nuclear bombs and are constantly exposed to unregulated chemicals that aren't even legal in many other countries. During a period when health costs are rising out of the affordable range for many Americans, it's time we found out whether these factors have anything in common.

 

My diagnosed autoimmune diseases include Graves' disease, celiac disease, pernicious anemia, and lichen sclerosis.

 

Comment 23

Idiopathic Interstitial Pneumonitis needs much more research to determine the cause. Specific medications need to be studied to determine which ones slow/stop the progress of deterioration in the lungs.

 

Comment 24

You can add me to the list of autoimmune disease as well. I was d/x with SJogrens four years ago and have been miserable ever since. I was told by my doctor it is barely even manageable and definitely not curable. It is so much more than just dryness. I come from a family of no known autoimmune diseases. I had a great-grandmother who lived to be 101 years and quality ones at that therefore it isn’t in the genes. Something else is going on and there isn’t a day that goes by that I am not trying to figure it out!

 

Comment 25

Hashimoto's here!! Thanks Karhu for the link!

 

Comment 26

My husband and I have both been diagnosed with Wegener's Granulomatosis, so we are a prime example and proof that autoimmune diseases do have an environmental cause. They tell us is it is almost unknown for a husband & wife to have WG that didn't meet via a support group. WG primarily affects the upper/lower respiratory tracts and also the kidneys but due to it's systemic nature can affect any part of the body but for us we are both affected in the upper respiratory tracts, thus indicating to me that it is something we are inhaling. I was EVENTUALLY diagnosed in 1999 and then my husband in 2006. We have been together for over 30 years. In 2006 Doctors said that there had to be an environmental cause to our illness but none would help us to find out what it was. So I began to research this subject myself and have done now for 5 years and have spoken via email to many eminent Doctors, Scientists, Professors, etc. through out the world who are doing research into environmental triggers for WG and other Autoimmune diseases and all have agreed with me. My conclusion is that in our case it is my husband's work exposures to wood dust and the chemicals therein. He is a woodworker/wood machinist working mainly with wood composite boards such as MDF, particle board/chipboard, wood cement board, etc. Research has shown that not only is Wood Dust per se a known human carcinogen (although they don't know as yet what element it is that renders it carcinogenic but I suggest it's the silica found naturally in all woods) but also these boards and their laminates, pvc veneers and protective coatings contain many, many toxic & carcinogenic chemicals that are harmful to humans and have already been linked to autoimmune disease such as silica, solvents, heavy metals and pesticides, wood preservatives, asbestos, etc. Water based pesticides used in many wood products, for example, have silica added to speed up ingestion by the pest by scratching the hard outer cuticle shell of the pest. This must be emitted in the dust produced by wood machinery and if it does this to hard shells of pests then what is it doing to the delicate tissues in our lungs, etc.? All woodworkers bring home this toxic dust to contaminate their and expose their families. Dust mask and protective clothing was rarely, if ever given to most woodworkers. Even today adequate PPE is not routinely given to all woodworkers and wood machinists who breath in this carcinogenic and toxic particulate/dust all day every day. This has to cause harm but due to long latency periods and seemingly vague initial symptoms i.e. chronic sinusitis, coughs/colds that won't go away, many wood workers fail to associate their ill health with their work exposure but by the time they do it's too late. So come on, wake up and smell the coffee or should I say the wood dust! Our environment is maiming, disabling and ultimately killing us but it doesn't have to be that way. I urge anyone with an autoimmune disease to think about possible past exposures at work or in the home. Tell your doctors & post on forums. The answer is there we just have to all look for it.

 

Comment 27

All carpeting and other man made floor coverings should be investigated in respect to the development of autism. Given the amount of time that infants, toddlers and young children spend crawling, playing, sitting or laying on the floor between the ages of a few months old until school age and that time period is also highly comparative to a child's main vaccination time which is so often noted as the time period that children start to demonstrate the first signs autism there appears to be a possible indicator that needs investigation. Submitted by Diane Zehnpfennig

 

Comment 28

Autoimmune diseases are on the rise and they are not well understood. Something environmental coupled with your genetic predisposition triggers your body to attack itself. The environmental trigger is where some prevention can happen! Lets study the environmental mechanisms.

 

Comment 29

Commentators here may find the Encyclopedia of Earth ( http://www.eoearth.org/ ) a valuable source of Public Health Statements on a variety of substances (go to Encyclopedia's Search Box and enter Public Health Statement).

 

Comment 30

vogelhn:

 

My case is probably typical for autoimmune occurrences that may possibly be stress related. I'm a US technologist living under constant job-related stress for the past 44 years, particularly the last 10. While travelling abroad on business at age 60, my lower body was attacked by CIDP. Within 3+ weeks I couldn't walk, my legs totally numb. It took regular treatments of IvIg plus 3 years of physical therapy to go from wheelchair-stricken to crutches, and then another 2 years of therapy to slowly walk using a cane. Both sides of my European lineage never had this ailment. I'm now 66 and consider myself lucky to be self-mobile, albeit with considerable difficulty.

 

Comment 31

I now have two autoimmune diseases. One being Thyroid and another some years later type I Diabetes. My body has turned on itself and taken my old life with it. I worked at a printing company prior to my thyroid disease for 7.5 years and inhaled many chemicals. The disease starting some months after leaving due to pregnancy. I returned 3 months later to the company and immediately became ill and was able to smell all chemicals which made me ill. I left and never returned. I became chemical sensitive to everything in my environment for two years. I still cannot handle certain smells. I firmly believe my inhaling all those chemicals at that printing company has made me ill and compromised my immune system and caused my immune system to attack itself... :(

 

Comment 32

A number of diseases and disease mechanisms which neither the research community nor the practice of medicine really understand today could be explained as autoimmune disorders of the system of circulating proteins in the bloodstream, brought on by immune system attacks which result from the presence of too much of a particular substance (the happen) on a particular binding site for enough longer than it normally takes the body to clear such exposures for the immune system to take notice (i.e. the complement system to act).

 

Answers will not be found in today's paradigm, in today's rules, any more than Pasteur did.

 

Comment 33

The research proposals on this website focus on possible environmental causes of autoimmune diseases, autism, chronic fatigue, chemical sensitivity/intolerance, military veterans ‘illnesses, as well as individuals who report symptoms associated with oil spills, fracking, hazardous waste sites, various community exposures, dioxin, home remodeling, poor indoor air quality, mold, pesticide use, and myriad other environmental exposures. But, in fact, individuals with these seemingly unrelated exposures and multi-system health problems share a great deal in common: their multi-system symptoms are often triggered by every day, low-level chemical exposures. Many also report adverse reactions to foods, medications, alcoholic beverages and/or caffeine. Dr. Nicholas Ashford of MIT and I first described this phenomenon 15 years ago. Toxicant-Induced Loss of Tolerance (TILT) is the name we gave to the underlying dynamic. It involves a two-step process whereby an initial acute or chronic toxic exposure causes loss of tolerance for everyday exposures. These new-onset intolerances perpetuate the disease process. We described how low-level exposures to common chemicals, foods, and medications may be the driving force behind the increased incidence of many hitherto unexplained medical symptoms and how masking—resulting from overlapping responses to multiple incidents—obscures the fact that everyday exposures can perpetuate illness. These concepts arose from reports by physicians, researchers and patients from more than a dozen industrialized nations. Collectively, their observations provide evidence that toxicant-induced loss of tolerance may be a new theory of disease. Currently, we are at the germ theory stage in terms of our understanding of this phenomenon. Well-founded theories—those based on careful observation, as in the case of the germ theory—are vital for developing shared scientific understanding and igniting future research.

 

In summary, it appears we are dealing with a two-stage disease process: (1) loss of tolerance resulting from an acute or chronic exposure event, followed by (2) repeated triggering of symptoms by everyday exposures, such as gasoline vapors, engine exhaust, fragrances or cleaning agents—exposures which had not been a problem for the person previously. This phenomenon became increasingly common with the widespread introduction of synthetic organic chemicals following WW II. This, coupled with the fact that 90% of Americans spend 90% of their day inside poorly ventilated structures where unprecedented types and levels of synthetic volatile organic chemicals (VOCs) are present, has led to the epidemic of chronic illnesses we are witnessing today. If we are to understand the extent to which these exposures contribute to the host of chronic illnesses mentioned on this website, doctors and researchers must have access to environmental medical research units— hospital-like research facilities in which people with major illnesses such as autism or autoimmune disorders, can be placed on an elimination diet in a chemically clean environment to see if their symptoms improve. If their symptoms resolve, then everyday exposures and foods can be reintroduced, one at a time. We are all so different and we respond differently to different exposures. NIEHS has an unprecedented opportunity: new approaches for assessing gene and protein expression and new brain imaging techniques can be used both before and after challenges in an EMU. We need to move forward, but not without this essential research tool—the Environmental Medical Unit (EMU). The EMU has been a priority recommendation of several professional and governmental conferences, yet still no research EMU exists in the U.S. It is time for NIEHS/NIH to add the EMU to its portfolio, so that we can all begin to understand the common dynamic shared by so many chronic, costly, and disabling medical conditions. The many excellent comments shared on this website testify to this need.

  1. Chemical Exposures: Low Levels and High Stakes by Nicholas A. Ashford and Claudia S. Miller (Wiley). May be downloaded at no charge from www.chemicalexposures.org, along with a published and validated screening questionnaire for chemical intolerance, the Quick Environmental Exposure and Sensitivity Inventory (QEESI).
  2. Toxicant-induced loss of tolerance—an emerging theory of disease? Miller CS. Environmental Health Perspectives: vol 105 Supp 2:445-453 (1997).
  3. Empirical approaches for the investigation of toxicant-induced loss of tolerance. Miller C, Ashford A, Doty R, Lamielle M, Otto D, Rahill A, Wallace L. Environmental Health Perspectives: vol 105 Supp 2:515-519 (1997).
  4. Toxicant-induced loss of tolerance. Miller CS. Addiction 96(1):115-139 (2000).

 

Comment 34

Dear NIEHS, during the last few moments on Central Time (6:35) I want to make a final comment regarding "Research on Chemical Sensitivities /Intolerances." Many of the people we have asked to vote have found "our" voting site DOWN with a red triangle at the corner. Many intelligent people who support us have failed to be able to get through the jumps and hoops required to simply elicit a vote. We are very loosely and poorly organized because we are the sickest group on this NIEHS competition.

 

Those of us who are well enough to use a computer employ the following group for updates on world issues regarding all the forms of toxins to which we already adversely react. Many/most of us also suffer from pre-natal effects of dioxin, one of the most widely fat-accumulated toxins, second only to the metabolite of DDT, called DDE found in the vast majority of those of us who can afford to pay for fat biopsies and blood work.

 

Go to WSMCSN@yahoogroups.com to become one of the people who realized 0-30 years ago, that we are polluting the environment, meaning our homes, our yards, our air, soil and water with toxic petrochemicals, drugs, and even toxic waste from smoking. OUTDOOR smoking is one of the big issues that keep us in our houses. PESTICIDE SPRAYING causes us unbelievable illness and loss of income. PERFUMES AND FRAGRANCES keep our children from attending school. Some of us are threated with loss of our children when they do get sick from the inevitable flood of toxins. In fact, if our children who are sick fail to attend public school OUR CHILDREN ARE TAKEN AWAY FROM US.

 

DO WE NEED RESEARCH NOW?

 

Please read just this week's research that MCS'ers read. Do something. We need research on our illness.

 

----------------------------------------------------

China smoking ban may have little effect. In a country of 300 million smokers, where many don't know of the health risks of tobacco, few expect much from a ban effective Sunday. Previous efforts to ban smoking in public places here have been plagued by false starts and failed campaigns. Los Angeles Times, California. http://lat.ms/jOOOfu 

 

Crude oil chemical linked to heart defect in babies. Babies who are exposed before birth to ethyl benzene, a toxic component in crude oil, may have a higher risk of developing congenital heart disease, US researchers said Saturday. Agence France-Presse http://bit.ly/mRECSC 

 

Stillbirths tied to secondhand smoke. Pregnant women who live or work with smokers may be at slightly higher risk of having a stillbirth, suggests a study that adds to evidence that even secondhand smoke can harm unborn babies. Reuters http://reut.rs/mxk4dw 

 

A new victim of second-hand smoking: Fish. With the world's smokers burning through a breathtaking 5.6 trillion cigarettes per year - 4.5 trillion of which are simply tossed away outside after they're smoked - little things add up fast. That, as it turns out, can be especially dangerous for one type of nonhuman critter: fish. Time Magazine http://ti.me/j636hq 

 

College students push to restrict bottled water. Bottled water: It's a vending machine's healthy alternative to sugary soda, a convenient way to hydrate on the go and, lately, a total faux pas on many college campuses. Washington Post http://wapo.st/lQAHw5 

 

The oil's story, from wellhead to beach. There is no story yet about the ultimate ecological damage last year's spill wrecked on the Gulf of Mexico. Early returns have seemed positive, but more systemic problems could appear. The spike in dolphin deaths could be tied to oil-derived chemicals. Turtle or crab growth could be stunted. It's too early to know. Greenwire http://nyti.ms/kSe1IB 

 

WHO takes on chronic disease. The World Health Organization focused for decades on infectious diseases, but now it's putting non-communicable diseases near the top of its agenda. Washington Post http://wapo.st/iHAEFn 

 

Groups call on BLM to act against Wyoming ozone. Environmentalists have asked regulators to consider slowing down the pace of gas drilling and other steps to curb air emissions in western Wyoming following several days of severe ozone pollution last winter. Associated Press http://bit.ly/iV2CYi

 

India has 11 years to ban endosulfan. A UN-backed regime of 173 countries on Friday agreed to globally "phase out" the farm insecticide endosulfan - a decision with significant implications for India, the world's largest manufacturer and user of the chemical. New Delhi Hindustan Times, India. http://bit.ly/lixFRS 

 

Weather chief draws flak over plea not to release radiation forecasts. The chief of the Meteorological Society of Japan has drawn flak from within the academic society over a request for member specialists to refrain from releasing forecasts on the spread of radioactive substances from the troubled Fukushima Daiichi nuclear plant. Mainichi Daily News, Japan. http://bit.ly/lq1QFU

 

Japan's unhelpful politics: Rebuilding Japan or ruining it. Whether the reconstruction council and nuclear investigation promote deep changes in the way things are done in Japan rests largely on the prime minister's powers of leadership. Economist http://econ.st/jyy4Gd 

 

One big obstacle to Japan's recovery? Trash. On the outskirts of the seaside city of Kesennuma, what was once a baseball field and park has been turned into at least two football fields' worth of garbage, piled 15 feet high. This is but a tiny fraction of Japan's tsunami-related debris. All Things Considered, NPR.  http://www.npr.org/templates/transcript/transcript.php?storyId=135770675 

 

Chubu Electric seeks restart of 'most dangerous' nuke plant. Chubu electric is proposing to restart a reactor at its Hamaoka nuclear power plant to help alleviate a possible summer power shortage – but local governments and residents are fiercely opposed to restarting the No. 3 reactor of what is described as "the world's most dangerous" nuclear power plant. Asahi Shimbun, Japan. http://bit.ly/lAABYG

 

Climate change could spawn more tornadoes. With this week's tornado outbreak in the South, as with any major weather disaster these days, people ask questions about its relation to the huge elephant that's lurking in the corner - global climate change. USA Today http://usat.ly/k2Olw0 

 

Obama appalled by tornado damage in Alabama. President Obama joined thousands of storm victims across the tornado-ravaged South on Friday in making his way past splintered houses along devastated streets, and he promised federal aid to help communities rebuild. Washington Post http://wapo.st/mSWcf9 

 

Scientists probe genetic component of climate-hardy species. Forest Service researchers are in the midst of teasing out which genes help Douglas firs and 39 other species of plants, animals and pathogens found in Western forests adapt to climate change. ClimateWire http://nyti.ms/mOkzcj 

 

Court rejects challenge to California's clean-car regs. A federal appeals court rejected a legal challenge Friday that sought to bar implementation of a California regulation meant to reduce greenhouse gas emissions by forcing automakers to make and sell less polluting cars in the state. Associated Press http://www.businessweek.com/ap/financialnews/D9MTIJFG0.htm 

 

TVA's Johnsonville plant shutdown fuels counties' job fears. TVA's game-changing plan to shut down parts of its coal-burning power production fleet will mean cleaner air for Middle Tennessee and elsewhere, but it has left at least one community in shock. Nashville Tennessean, Tennessee. http://article.wn.com/view/2011/04/30/TVAs_Johnsonville_plant_shutdown_fuels_counties_job_fears/ 

 

EPA revisits rules on streams. The Ohio EPA is planning to change its approach to curbing threats to the state's network of rivers, creeks, wetlands and lakes through tougher pollution limits for sewage-treatment plants and a new process to protect and repair streams threatened by proposed strip mines, roads and housing subdivisions. Columbus Dispatch, Ohio. http://bit.ly/mR67x9 

 

Cancer cluster research continues. Five children in southeastern St. Clair County have been diagnosed with a rare form of kidney cancer in the past four years, and officials are trying to find out why. The answer so far: They're investigating. Port Huron Times Herald, Michigan. http://bit.ly/lGkN3Y 

 

Residents tested for pesticide. Anti-pesticide activists brought more than complaints to a state Board of Forestry meeting. Triangle Lake residents, who for years have been fighting aerial spraying of herbicides on the timbered slopes around their homes, came with data that showed two herbicides in the urine of 21 community members, including children. Eugene Register Guard, Oregon. http://bit.ly/inr6zu 

 

Cairo, Illinois, argues for its life in levee breach plan; others protest. Once the stuff of literary references, blues lyrics and steamboat culture, now Cairo is a dilapidated intersection of two rivers and three states, marked by poverty and decay. Now – as floodwater rises around it - the town has become the center of a debate. Why save a dying town? St. Louis Post-Dispatch, Missouri. http://bit.ly/iMpeDi 

 

Anxious eyes on a river as flooding threat looms. Major General Michael J. Walsh is likely to make a lot of people angry over the next few days. But which group of people is not so clear. It will depend on whether he decides to flood farmland in Missouri in order to save a town in Illinois from the ravages of the rising Mississippi and Ohio Rivers. New York Times http://nyti.ms/jHYnrk 

 

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Idea 11: Epigenome modulation by environmental factors

The modulation of the epigenome by environmental factors represents a major mechanism for trans-generational effects imparted by chemical, physical and biological agents.

Idea 12: Exploiting toxicological mechanisms for therapeutic benefit

Mechanisms by which certain toxicants are delivered can be used as the basis for developing new methods or pathways for delivering drugs to sites/tissues/subcellular organelles.  When coupled to optimized methods for activation or inactivation, these delivered drugs can be optimized for specific intervention strategies.  Basic science can therefore be translated into useful products and processes.

Idea 13: Genetic susceptibility to environmental influences

A critical move toward personalized prevention and medicine approaches is to identify genetic and other individual level factors that moderate the effects of the environment (physical and psychosocial) on physical and behavioral health.


Comment

Examples include the greater susceptibility of Caucasians to sunburn, the greater susceptibility of blacks to vitamin D deficiency, the 1% incidence of lathyrism.  It is well known that some individuals tolerate toxic insults others do not. Understanding the basics of why this is so may eventually provide for generalizable advice regarding who is more likely to react badly to a given environmental insult or medical challenge with a particular drug.

Idea 14: Life-stage approach

Research is need to better understand the nature and extent of lifestage susceptibility - in terms of differences in toxicokinetics, toxicodynamics (including critical windows), exposure, later life implications of early life exposures (Barker hypothesis).

Idea 15: Mapping the human toxome

Historically, the main method for ascertaining the toxicological risk of new drug candidates and chemicals has been through the use of animal models for toxicity testing. Animal models are often not predictive of human toxicity, can be expensive, time consuming, and pose ethical issues due to potential pain and distress to animals. We are proposing a new approach as the foundation for a human toxicology project. This approach (referred to as an integrated systems toxicology approach) takes advantage of the exploding scientific knowledge of mode of action in target cells, tissues and organs that is being driven by advances in molecular and computational tools, coupled with the concomitant development of high-throughput and high-content screening assays that allow interrogation of pathways, to develop a more accurate, predictive, cost effective, and efficient means for predicting toxicity in humans. A number of pathways have already been identified; however, most are only partially known and no common annotation exists. Mapping the entirety of these pathways (i.e. the Human Toxome) will be a large-scale effort, perhaps on the order of the Human Genome Project.  A project of this magnitude will require long-term and sustained funding and will require a consortium effort that brings together expertise that currently resides in a number of government and regulatory agencies, industry, and academics.  Ultimately these investments promote public health and safety but also stimulate the economy, creating jobs and global economic competitiveness.


Comment

Why not use both approaches?

Idea 16: Multi-pollutant exposures

We need to better understand multiple concurrent exposures, because that's the way humans are exposed in the real world.  We currently do not consider these in an integrated biological way, and even the statistical machinery to process and evaluate observations is lacking.


Comment 1

Yes—Good Idea

 

Besides giving a Patient an Anti Biotic or an Anti Viral for an Illness---I would also want to know all the Stressors that caused the Illness.  The Navaho Medicine Man used to Treat the Whole Community besides the Patient. 

 

I would like the Patient to list all the Stressors in the House and the Environment.  So when a patient sees a Doctor they might be given a questioner that asks---Do you drink contaminated Well Water?---Is Your Air Contaminated?---Do you live by a Hibernian Plant?---Is there Clusters of Illnesses in your Community?----Do you live by a Mercury or Lead Factory?---Do you live by a Coal Powered Electric Plant?---Do you live by a Freeway?---Do you Recycle and leave Beverage Bottles that could contain Mold?---Does your Home have Mold?---Do you live by a Toxic River?---Do you live in a Farm Community that DDT was Used?---When and Where do your Allergies Flare Up?


Comment 2

I write to suggest that this topic is a very substantial idea that should be integrated with the Visionary Idea presented by Mary Lameille "Research on Chemical Sensitivities, Intolerances" that is currently running in first place at this same NIEHS website. I believe that some of the ideas presented are overlapping with the idea in quotes above. I myself, have been sick for 25 years and it was only because a doctor referred me to an Environmental Ecologist that I understood the mechanisms that were causing weight loss, inability to eat, neurological symptoms, menstrual disregulation, thyroid disorder, etc. I had been exposed to a host of chemicals and carried inoculation-borne viruses that have both since been treated by the proper non-mainstream doctors at Cedars Sinai, Johns Hopkins, and by Dr. Rea in Dallas, TX. Hope we can combine the votes that you have received with "Research on Chemical Sensitivities/Intolerances." Please contact me and I will help with the effort. jannarone@aol.com Thanks!


Comment 3

The research proposals on this website focus on possible environmental causes of autoimmune diseases, autism, chronic fatigue, chemical sensitivity/intolerance, military veterans’ illnesses, as well as individuals who report symptoms associated with oil spills, fracking, hazardous waste sites, various community exposures, dioxin, home remodeling, poor indoor air quality, mold, pesticide use, and myriad other environmental exposures. But, in fact, individuals with these seemingly unrelated exposures and multi-system health problems share a great deal in common: their multi-system symptoms are often triggered by every day, low-level chemical exposures. Many also report adverse reactions to foods, medications, alcoholic beverages and/or caffeine. Dr. Nicholas Ashford of MIT and I first described this phenomenon 15 years ago. Toxicant-Induced Loss of Tolerance (TILT) is the name we gave to the underlying dynamic. It involves a two-step process whereby an initial acute or chronic toxic exposure causes loss of tolerance for everyday exposures. These new-onset intolerances perpetuate the disease process. We described how low-level exposures to common chemicals, foods, and medications may be the driving force behind the increased incidence of many hitherto unexplained medical symptoms and how masking—resulting from overlapping responses to multiple incidents—obscures the fact that everyday exposures can perpetuate illness. These concepts arose from reports by physicians, researchers and patients from more than a dozen industrialized nations. Collectively, their observations provide evidence that toxicant-induced loss of tolerance may be a new theory of disease. Currently, we are at the germ theory stage in terms of our understanding of this phenomenon. Well-founded theories—those based on careful observation, as in the case of the germ theory—are vital for developing shared scientific understanding and igniting future research.

 

In summary, it appears we are dealing with a two-stage disease process: (1) loss of tolerance resulting from an acute or chronic exposure event, followed by (2) repeated triggering of symptoms by everyday exposures, such as gasoline vapors, engine exhaust, fragrances or cleaning agents—exposures which had not been a problem for the person previously. This phenomenon became increasingly common with the widespread introduction of synthetic organic chemicals following WW II. This, coupled with the fact that 90% of Americans spend 90% of their day inside poorly ventilated structures where unprecedented types and levels of synthetic volatile organic chemicals (VOCs) are present, has led to the epidemic of chronic illnesses we are witnessing today. If we are to understand the extent to which these exposures contribute to the host of chronic illnesses mentioned on this website, doctors and researchers must have access to environmental medical research units— hospital-like research facilities in which people with major illnesses such as autism or autoimmune disorders, can be placed on an elimination diet in a chemically clean environment to see if their symptoms improve. If their symptoms resolve, then everyday exposures and foods can be reintroduced, one at a time. We are all so different and we respond differently to different exposures. NIEHS has an unprecedented opportunity: new approaches for assessing gene and protein expression and new brain imaging techniques can be used both before and after challenges in an EMU. We need to move forward, but not without this essential research tool—the Environmental Medical Unit (EMU). The EMU has been a priority recommendation of several professional and governmental conferences, yet still no research EMU exists in the U.S. It is time for NIEHS/NIH to add the EMU to its portfolio,

 

so that we can all begin to understand the common dynamic shared by so many chronic, costly, and disabling medical conditions. The many excellent comments shared on this website testify to this need.

  1. Chemical Exposures: Low Levels and High Stakes by Nicholas A. Ashford and Claudia S. Miller (Wiley). May be downloaded at no charge from www.chemicalexposures.org, along with a published and validated screening questionnaire for chemical intolerance, the Quick Environmental Exposure and Sensitivity Inventory (QEESI).
  2. Toxicant-induced loss of tolerance—an emerging theory of disease? Miller CS. Environmental Health Perspectives: vol 105 Supp 2:445-453 (1997).
  3. Empirical approaches for the investigation of toxicant-induced loss of tolerance. Miller C, Ashford A, Doty R, Lamielle M, Otto D, Rahill A, Wallace L. Environmental Health Perspectives: vol 105 Supp 2:515-519 (1997).
  4. Toxicant-induced loss of tolerance. Miller CS. Addiction 96(1):115-139 (2000).

Idea 16: Multi-pollutant exposures

We need to better understand multiple concurrent exposures, because that's the way humans are exposed in the real world.  We currently do not consider these in an integrated biological way, and even the statistical machinery to process and evaluate observations is lacking.


Comment 1

Yes—Good Idea

 

Besides giving a Patient an Anti Biotic or an Anti Viral for an Illness---I would also want to know all the Stressors that caused the Illness.  The Navaho Medicine Man used to Treat the Whole Community besides the Patient. 

 

I would like the Patient to list all the Stressors in the House and the Environment.  So when a patient sees a Doctor they might be given a questioner that asks---Do you drink contaminated Well Water?---Is Your Air Contaminated?---Do you live by a Hibernian Plant?---Is there Clusters of Illnesses in your Community?----Do you live by a Mercury or Lead Factory?---Do you live by a Coal Powered Electric Plant?---Do you live by a Freeway?---Do you Recycle and leave Beverage Bottles that could contain Mold?---Does your Home have Mold?---Do you live by a Toxic River?---Do you live in a Farm Community that DDT was Used?---When and Where do your Allergies Flare Up?


Comment 2

I write to suggest that this topic is a very substantial idea that should be integrated with the Visionary Idea presented by Mary Lameille "Research on Chemical Sensitivities, Intolerances" that is currently running in first place at this same NIEHS website. I believe that some of the ideas presented are overlapping with the idea in quotes above. I myself, have been sick for 25 years and it was only because a doctor referred me to an Environmental Ecologist that I understood the mechanisms that were causing weight loss, inability to eat, neurological symptoms, menstrual disregulation, thyroid disorder, etc. I had been exposed to a host of chemicals and carried inoculation-borne viruses that have both since been treated by the proper non-mainstream doctors at Cedars Sinai, Johns Hopkins, and by Dr. Rea in Dallas, TX. Hope we can combine the votes that you have received with "Research on Chemical Sensitivities/Intolerances." Please contact me and I will help with the effort. jannarone@aol.com Thanks!


Comment 3

The research proposals on this website focus on possible environmental causes of autoimmune diseases, autism, chronic fatigue, chemical sensitivity/intolerance, military veterans’ illnesses, as well as individuals who report symptoms associated with oil spills, fracking, hazardous waste sites, various community exposures, dioxin, home remodeling, poor indoor air quality, mold, pesticide use, and myriad other environmental exposures. But, in fact, individuals with these seemingly unrelated exposures and multi-system health problems share a great deal in common: their multi-system symptoms are often triggered by every day, low-level chemical exposures. Many also report adverse reactions to foods, medications, alcoholic beverages and/or caffeine. Dr. Nicholas Ashford of MIT and I first described this phenomenon 15 years ago. Toxicant-Induced Loss of Tolerance (TILT) is the name we gave to the underlying dynamic. It involves a two-step process whereby an initial acute or chronic toxic exposure causes loss of tolerance for everyday exposures. These new-onset intolerances perpetuate the disease process. We described how low-level exposures to common chemicals, foods, and medications may be the driving force behind the increased incidence of many hitherto unexplained medical symptoms and how masking—resulting from overlapping responses to multiple incidents—obscures the fact that everyday exposures can perpetuate illness. These concepts arose from reports by physicians, researchers and patients from more than a dozen industrialized nations. Collectively, their observations provide evidence that toxicant-induced loss of tolerance may be a new theory of disease. Currently, we are at the germ theory stage in terms of our understanding of this phenomenon. Well-founded theories—those based on careful observation, as in the case of the germ theory—are vital for developing shared scientific understanding and igniting future research.

 

In summary, it appears we are dealing with a two-stage disease process: (1) loss of tolerance resulting from an acute or chronic exposure event, followed by (2) repeated triggering of symptoms by everyday exposures, such as gasoline vapors, engine exhaust, fragrances or cleaning agents—exposures which had not been a problem for the person previously. This phenomenon became increasingly common with the widespread introduction of synthetic organic chemicals following WW II. This, coupled with the fact that 90% of Americans spend 90% of their day inside poorly ventilated structures where unprecedented types and levels of synthetic volatile organic chemicals (VOCs) are present, has led to the epidemic of chronic illnesses we are witnessing today. If we are to understand the extent to which these exposures contribute to the host of chronic illnesses mentioned on this website, doctors and researchers must have access to environmental medical research units— hospital-like research facilities in which people with major illnesses such as autism or autoimmune disorders, can be placed on an elimination diet in a chemically clean environment to see if their symptoms improve. If their symptoms resolve, then everyday exposures and foods can be reintroduced, one at a time. We are all so different and we respond differently to different exposures. NIEHS has an unprecedented opportunity: new approaches for assessing gene and protein expression and new brain imaging techniques can be used both before and after challenges in an EMU. We need to move forward, but not without this essential research tool—the Environmental Medical Unit (EMU). The EMU has been a priority recommendation of several professional and governmental conferences, yet still no research EMU exists in the U.S. It is time for NIEHS/NIH to add the EMU to its portfolio,

 

so that we can all begin to understand the common dynamic shared by so many chronic, costly, and disabling medical conditions. The many excellent comments shared on this website testify to this need.

  1. Chemical Exposures: Low Levels and High Stakes by Nicholas A. Ashford and Claudia S. Miller (Wiley). May be downloaded at no charge from www.chemicalexposures.org, along with a published and validated screening questionnaire for chemical intolerance, the Quick Environmental Exposure and Sensitivity Inventory (QEESI).
  2. Toxicant-induced loss of tolerance—an emerging theory of disease? Miller CS. Environmental Health Perspectives: vol 105 Supp 2:445-453 (1997).
  3. Empirical approaches for the investigation of toxicant-induced loss of tolerance. Miller C, Ashford A, Doty R, Lamielle M, Otto D, Rahill A, Wallace L. Environmental Health Perspectives: vol 105 Supp 2:515-519 (1997).
  4. Toxicant-induced loss of tolerance. Miller CS. Addiction 96(1):115-139 (2000).

Idea 17: Need for animal and epi studies reflecting real human conditions

Currently animal models focus on studies of single chemical exposures, models which have little relevance to the human environment  and may therefore be misleading with respect to not only consequences of exposure, but associated risk levels.
Similarly, epidemiological studies focus primarily on main effects, when important interactions that may identify vulnerability are 'statistically controlled'. Given our understanding that most human diseases and disorders are complex in nature, i.e., arise from multiple etiologies, most toxicology studies miss the mark. Current approaches may underestimate the actual contributions of chemicals to human diseases and disorders, or miss interactions that may have mitigation potential


Comment 1

If we can develop statistical applications to analyze microarray data, why can we not support the development of methods to model multiple exposures and health outcomes?  Grant reviewers are not receptive to projects that propose studying exposure to multiple contaminants, such as the mountaintop mining communities in WVA and KY.


Comment 2

I would support this concept but would also emphasize that in order to do this there is a critical need to develop and integrate endpoint assessments that are more sensitive and reflect more recent scientific understanding of organ systems, disease processes, etc.  To have animal or Epi studies reflect more accurately human exposure we need to have sensitive endpoints and a battery of endpoints to be able to adequately assess adverse effects.

Idea 18: Often overlooked

The brain-body neurological connection. Cervical spines very often twist and are putting abnormal pressure on the spinal cord. Proper chiropractic analysis and adjustments should always be included.

Idea 19: Oxidative stress and the etiology and progression of diseases

It is increasingly recognized that the expression and development of most if not all human diseases are influenced by environmental agents or conditions that influence either susceptibility to the disease, rate of disease progression, or extent of resolution.  In my view, defining the underlying cellular and molecular mechanisms for these changes in disease progression and outcome will provide both the greatest opportunity and the greatest challenges for the environmental health scientists in the future.  Rarely is there a single disease endpoint or a single etiologic factor in human disease, and likewise, humans are rarely exposed to a single toxin or toxicant.  Complex mixture exposures can result in multiple health outcomes that may influence multiple disease states simultaneously, particularly in elderly individuals that are often struggling with multiple diseases.  A cellular and molecular mechanistic understanding of how compounds and mixtures affect health status will provide guidance for risk assessment, disease prevention, and therapeutic strategies.  At the cellular level, oxidative stress and inflammation appear to be central pathophysiologic responses that underpin the biological consequences of exposure to a wide variety of agents in disease states, and it will be valuable to study these responses in more detail.

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