Seattle-Tacoma International Airport - Medical Issues

Seattle-Tacoma International Airport, Third Runway,Sea Tac, Washington

Examination of the impact of the Seattle-Tacoma International Airport on the region poses a number of analytic challenges.  In a previous blog article, Seattle-Tacoma International Airport - Pollution, I discussed pollution issues.  Links to my other blog issues on the airport may be found listed below.

The focus of this blog article is on health related issues which may be related to airport operations, keeping in mind that there are other sources of pollution that may contribute to health conditions, and that there are factors other than environmental conditions which may contribute to health conditions.

Other sources of pollution may include vehicular traffic, such as cars, trucks, vans, buses and rail systems, as well as industry and commerce as well as other human activity such as wood burning. Many factors, in addition to pollutants, contribute to health.  Economic and sociological factors such as poverty, education and disenfranchisement all are factors which influence health.

There is considerable information available from the King County Health Department on the geographical distribution of various medical conditions.  These are listed below. Incidences of cancer, respiratory disease, cardiac and pulmonary heart conditions vary throughout the county.

MEDICAL ISSUES

Known

• A number of medical conditions may be impacted by environmental factors, including cancer, respiratory/pulmonary,sleep disorders,  blood/vascular disorders, immune system disorders, cardiac disorders and neurological/psychiatric/psychological issues that can emerge as a result of increased environmental exposure. The impact of air pollution on the generation of reactive species such as oxygen and other radicals may also adversely impact sleep states.
• Environmental pollutants often increase generation of reactive species or oxygen radicals, increasing oxidative stress, impacting a number of medical conditions, and may create new ones.
• Electromagnetic fields (microwaves) - Potential effects vary according to the distance from the source with general public exposure lessened.  Health effects studied include cancer, physiological and thermoregulatory responses, reproductive issues, cataracts, and impacts on calcium ion mobility.  Effects have not been sufficiently established to be able to determine regulatory standards.
• Studies have been made by the Washington State Department of Health on glioblastoma multiforme and other conditions.
• A February 25, 1999 report from the State Health Department and King County Health Department indicates: "While the state health department found that the occurrence of all SeaTac Concerned Citizen cancers in the area within 5 miles of the airport was less than expected in comparison to King County, the Seattle-King County health assessment found an increase in cancer deaths around SeaTac Airport."  This study examines health issues in the neighboring communities around the airport.
• There are extensive studies from the King County Department of Public Health available regarding a variety of health and socioeconomic factors for the communities in King County. These reports indicate increased incidence of cancer and pulmonary disease, but decreased risk of heart attack, stroke and Alzheimers relative to other areas.  There is also a higher degree of cigarette smoking in the region, complicating analysis.  There is a range of socioeconomic indicators showing lower socioeconomic indicators in the region.

Past Legacy

• One of the cardinal features of evolution is the incorporation of biologicals and minerals into a system in order to advance features that have evolutionary advantage.  This is called biomineralization.  It is not inconceivable that out of the many molecules emitted through airport operations (and other sources throughout the region), that one in the witches brew of combinations might find a home within the human body, evolving the system, or throwing a monkey wrench into it. Calcite enabled the creation of the eye in trilobytes  in the pre-Cambrian.  However a serious problem in this process is the issue of interoperability between systems in such processes.
• To what extent does the ground on which we sit impact health?  The area holds the legacy of the ASARCO Tacoma Smelter Plume  formed in 1899, and the emissions since that period.  This legacy impacts rock, soil, water and air.  The Seattle-Tacoma International airport sits on a considerable amount of fill, which is in addition any deposition that may have fell on the underlying soil.  Other parts of the region may also have been impacted by sand, rock and gravel transported from sites more heavily impacted by the ASARCO Smelter's operations.
• The airport sits on Fraser Glaciation,  Vashon Stade.  To what extent do the rocks around the airport and the water affect health? It is possible that the area of the airport could hold some clue to past evolution.  A sloth was discovered in a swampy area north of the airport in 1961, and a mammoth tusk was discovered in the South Lake Union area of Seattle. Both sit at the Burke Museum.  DNA analysis from an archaeological find could perhaps provide scientists with clues to help solve emerging problems germane to our evolution and our ancestors.

Emerging or Unknown

• The emergence of new and novel health risks may occur in the witch's brew of chemical soup surrounding the airport and other areas subject to environmental risk. Illnesses that normally occur in other areas of the world may emerge in this arena, given the geological milieu in which the airport sits, the meteorological conditions, and the increased levels of pollutants, including carbon dioxide.  Carbon dioxide is a sensitive indicator of global warming and climate change and may also impact the respiratory system in a similar fashion in the immediate neighborhood of the airport.
• Seasonal flu and emerging viruses, could recombine in the environment surrounding the airport, mixing human and bird migration patterns with environmental factors impacting local populations.  Thus viruses could serve as a vector for the incorporation of novel or emerging features resulting from the witches brew of chemicals.
• Chemicals emitted in the witches brew of chemical emitted from airport operations could be impacted by solar radiation, a source of energy, especially during periods of geomagnetic storms.  Potentially subatomic collisions could evoke a transitional state in molecules, and be incorporated into the body.  Any impact from the creation of transitional molecules would be in addition to any direct effect from any solar storms.
• The witches brew of chemicals emitted by air transport, given the power, acceleration, deceleration and forces put on aircraft engines, abrasion, means that more exotic chemicals may be created.  However, it is possible that similar types of reactions may also be occurring in different parts of the region, perhaps to a different extent.

Establishing Correlations between Pollutants and Medical Conditions

• While some pollutants in particular are points of focus, the extensive lists provided make it difficult to correlate exposures to any one or any combination of health outcomes.  This is an issue of multiple correlation analysis in the face of numerous variables and outcomes, many of which may interact with each other to alter individual correlation between any two variables. 
• Analysis of risk focuses on cancer metrics.  While the emergence of the cancer risk is important (and critical), identification of other outcomes is also important. Early indicators of future outcomes may serve as helpful markers of environmental distress before its impact becomes too severe.
• Environmental markers might include blood coagulation measurements, markers for the impact of oxidative stress, markes for nuclear DNA and mtDNA damage, and markers for the preference of glycolysis in cells (Warburg Hypothesis), among other things.
• Categorization of medical systems, or medical coding, puts medical conditions in "boxes" which may make analysis difficult when causes and/or outcomes cross boundaries, medical conditions are inappropriately categorized or new information informs medicine.
• The division of conditions into physiological versus psychological causes presents such difficulties, especially when these conditions are subject to such a wide disparity of treatment throughout the existing sociological framework. The bifurcation of conditions into physiological versus behavioral outcomes tends to create categories that diminish or ignore the health and sociological impact of pollution exposure and/or cross category lines.
• Some indices that represent psychological stress may combine various psychological indicators in a weighting formula that may impede the ability to do correlation analysis on any one factor. One is left with memories of Upton Sinclair's "The Jungle", a book about meat packing plants, wondering how the whole was constructed from the parts.   Thus, the question remains in indices and tests as to whether the manner in which the indices are constructed drive a certain result or whether indices keep pace with changes in their individual components.
• Occupational and environmental health outcomes are not appropriately measured in a manner that can express the full continuum of types of work that exists in the sociological sphere.  This reflects the existing dysfunctional definitions of work and disability, and impacts correlation analysis between occupational and environmental health.
• Medical fields studying intersecting fields of study, such as neurology, psychiatry and psychology can come into conflict at times, making it more difficult to study health outcomes emerging from environmental factors. 
• Definitions based on subjective issues such as behavior and, belief systems, emerge to complicate the analysis of the impacts of environmental pollutants.
• The drive to cut medical costs conflicts with testing the impacts of increased environmental load on the public, leaving the impacts uncertain and placing the burden on those impacted. 
• Increased population and economic activity has impacted Western Washington so that environmental risk exists in many places throughout the region, to varying degree.
• The medical system currently does not provide sufficient support to provide both testing and treatment of medical conditions which may arise from the increased exposure to environmental pathogens. There are barriers to entry into the medical system which impede the ability to measure outcomes and protect human test subjects in the evolutionary process.
• Assessment of different contributors to morbidity and mortality may confound research into the underlying environmental issues.  An example of this is assessing the contribution of smoking to morbidity and mortality versus the environmental effects caused by airport operations.
• Different statistical measures may be used by reports, confusing the reader or making it difficult to interpret data shown in different forms;  Data may be presented with an incidence rate (occurrence of a condition in a population over a period of time), a prevalence rate (percentage of a population having a condition at a specific period of time) or mortality rate (percentage of deaths in a population over a period of time).  The US Government publishes data on morbidity and mortality .

The challenge is to put together to what extent the environmental factors drive the medical and  socioeconomic factors and are in turn influenced by them, in a positive feedback loop.

Sources:
Puget Sound Clean Air Agency - Final Report - Puget Sound Air Toxics Evaluation - October 2003
Department of Ecology - Toxic Cleanup Program (ASARCO Smelter Plume)
World Health Organization - Electromagnetic Fields
Port of Seattle - Part 150 Study
Port of Seattle - Groundwater Monitoring
Port of Seattle - Stormwater Pollution Prevention Plan
Scandanavian Journal of Health - Glioblastoma Multiforme
Tacoma Smelter Plume Information - Washington Department of Ecology
King County Community Health Indicators - King County (Top 10 Leading Causes of Death)
King County Public Health -School District Health Profiles
King County Health Profile
King County Public Health - Data and Reports

Blog Articles:
Externalities and Risk - The Seattle-Tacoma International Airport
Seattle-Tacoma International Airport - Environmental Issues
Seattle-Tacoma International Airport - Pollution

Climate Change and Global Health

Storm Surge Flooding, Westport, Washington, November 2009

Climate Change and Global Health

Climate change poses a number of risks to global health.  These risks draw our attention to the fact that health issues operate on a scale that transcends our own individual concerns, extending well beyond local communities, state and national boundaries.  

I attended a lecture in February, 2011, by Dr Howard Frumkin, Dean of the University of Washington School of Public Health on the health risks of climate change.  It was an interesting talk, covering many areas where climate change impacts global health. These impacts may be associated with the increased frequency of extreme weather events. 

Extreme weather events discussed included increased heat, cold, melting, freezing, flooding and droughts.  Increased atmospheric instability may give rise to more frequent hurricanes and tornadoes. Extreme weather events can be viewed on various time scales, from 50 to 100 year storms, to events on a more geological time scale.

Heat stress is of particular concern to the elderly, the young and the immune-compromised. Extreme heat, especially in non or inadequately air-conditioned spaces may result in premature mortality during heat waves, in the vulnerable, especially in the city where paved areas draw heat.  Dr Frumkin was concerned about the "harvesting" effect of heat waves on elderly, urban, populations.

Cold, snow, ice and freezing also may become survivability issues, involving issues of heating and interruption of water and electrical service.  Storms may impact travel and thus food supply, transportation of vital supplies to population centers and medical facilities.  

Public health challenges may emerge with air or water quality issues, impacting respiratory, cardiovascular, and other associated systems.  Infectious diseases may spread via the air or water through vectors  such as tic or mosquitoes, or via zoonotic means through human to animal or animal to human spread).  Allergies may develop in response to climate changes, and new pathogens may emerge or spread to different areas.

Air pollution is a problem which affects more than just urban areas.  With experience working in the regulatory air quality sector, I realize the widespread impacts that pollutants such as ozone and other pollutants have.  Photochemical reactions involving products of combustion (e.g. auto exhaust) take place in the atmosphere resulting in ozone levels downwind of major urban areas. As the reactions involve sunlight and heat, the levels on sunny and hot days increase in the summer. In the fall and spring periods of extended air stagnation resulting from stalled high pressure weather systems may increase the respiratory and cardiovascular burden on the vulnerable patient group. Air pollution does not know boundaries, thus residential and industrial pollution from other countries may impact us, as ours impacts theirs.  Forest fires add to the impact.  Extreme weather may impact all these issues.

The impact of climate change, extreme weather events and public health challenges may impact food production, may result in civil conflict, dislocation of impacted people and may increase the expression of mental health issues .

The discussion of climate science drives the discussion on public health impacts as projections are made regarding the manner in which changes will take place in Earth's climate systems.  Modeling climate systems drives downstream weather and public health challenges. These challenges are studied in a variety of settings, including federal government institutions such as NOAA, NASA and the CDC, and at a variety of state and local governmental and, at private institutions.  The Intergovernmental Panel of Climate Change and the National Climate Assessment have comprehensive plans reflecting policy in this area.

Extreme weather events can result in significant mortality and morbidity, as well as impacts to property.  Tornadoes and Hurricanes and wind storms may result in death and injuries from flying objects, falling trees and power lines as well as medical emergencies secondary to the event.  Fires may result from damaged gas lines. 

Increased flooding and storm surge may result in drownings and damage to property. Flooding may increased the spread of infectious diseases, problems with sewage systems and interruptions in drinking supplies

Drought may bring about reductions in food supply.  This is a serious issue as crops may be challenged to grow in areas where they were previously able to.  Vegetation, vectors and pathogens may spread into other areas as a result of warming.  This impacts the latitude at which such impacts occur as well as the altitude above sea level, moving to cooler latitudes and elevations.

More weeds may develop in urban areas in response to climate change and global warming as vegetation adjusts to the changing environment.

Extreme weather events thus may have public health impacts relating to many systems, resulting in dislocation of people and mental health issues as citizens adjust to the events.

The challenge is how to address climate change issues in the context of these public health issues.

Ebola

Raudfjorden Beach, Svalbard, Norway

The Ebola outbreak has proven to a challenge for worldwide heatlh leaders.  The CDC has information about Ebola on its website, as does the World Health Organization (WHO).  The CDC information is delineated into a number of topical areas of interest to subject audiences.  I'm interested in the etiology of Ebola, its transmission, and issues surrounding its current outbreak.

My interest in Ebola began during my actuarial career, reading the "Hot Zone" , a 1994 non-fiction book about incidents involving viral hemorrhagic fevers, including ebolaviruses and marbug viruses. The memory of the book stayed with me since I was reading it while sailing down the west coast of Vancouver Island in 15 foot swells in a sailing vessel.  I can recall eating copious amounts of ginger cookies to ward off seasickness as I read of hemorrhagic fevers killing off people very quickly, in a very bloody and gory fashion, as all the while I was lurching back and forth in the sea and swell on the Pacific Ocean.  The ginger cookies did their job and the memory is etched in my experience, gone but not forgotten, as Ebola emerges again, this time, expressed  in the news of an outbreak.

These hemorrhagic diseases killed off people before they had a chance to spread extensively, and, were confined to certain areas in Africa and mostly away from major population centers.

According to the CDC, the virus can be spread through direct contact with blood and body fluids of a person infected with Ebola, with objects such as syringes infected with Ebola and infected fruit bats or primates.  The question remains as to factors impacting the geographical distribution of Ebola, how it independently arises, factors of etiology and its potential spread elsewhere.

The recent upswing in the Ebola virus prompted me to question its etiology, transmission and other issues.  For example, because of the increase in number of cases, I wondered if the virus had recombined with another virus to increase its transmission and decrease its mortality, or if there were other factors.   In this blog article I consider a number of issues, and raise some questions relating to the virus.


Etiology

• Does Ebola predate the AIDs/SIV/HIV viruses and does it provide some idea of the origin of these viruses? The CDC expresses that it does not know the origin of the original host of the Ebola Virus;  It is interesting to study the context of the Ebola virus regarding its emergence out of the Kinshasha Highway  across the Congo into Uganda as discussed in "The Hot Zone".  Did the virus have origins in bat habitats such as caves, rock, lava tubes, environments exposed to varying bacteria and archaea?
• The Ebola virus is a negative sense RNA virus. The production of proteins from a negative sense RNA virus require first the production of Messenger RNA (mRNA) and then proteins from mRNA. Ebola does not have reverse transcriptase, which would ordinarily be needed to enable insertion of its genetic contents into the DNA.   Is its 'purpose' then to directly produce mRNA (messenger RNA), and why? Research has shown that the filoviruses behind Ebola are very old and that there is direct insertion of genetic content with indications of evolutionary divergence a long time ago.  - The Lin Edwards article, "Ebola and Marburg viruses may be much older than thought" discusses this subject.
• Does the Ebola virus relate to issues concerning New World Monkeys and Old World Monkeys and the divergence of the two species?  If so, would this tend to indicate the same type of environmental conditions that may have existed at the time of that divergence?
• What is the distribution of the virus?  Does the virus act with regards to specific populations, affecting certain populations in a negative or positive way, and leaving others untouched.  What factors in these populations would account for the outbreak?  Are other populations at risk?

Transmission

• Did the Ebola virus recombine with another virus (for example the Corona Mers Virus  , Seasonal Flu Virus or enteroviruses) to allow it to decrease its mortality rate and increase its transmission?  Is it continuing to do so and would further recombination with the current seasonal flu change it further along these lines? 
• A subject of interest to is transmission of Ebola from the natural host to a target population.  Is Ebola being expressed, sustained within the target population or being sequestered?  Does this imply sequestration in a host for transmission or expression later under circumstances that may enable it to be used as a regulatory operator or a mediator of group identity or expression of  immunity systems?  Is it developing a symbiotic relationship with the host or another virus in a toxin/anti-toxin sort of manner (discussed by my blog article on Dr Luis Villarreal and his work on group identity systems)? How does this concept explain the existence of this virus in a reservoir species?
• What is the risk for the spread of Ebola?  To what extent is the risk environmental and to what extent can it be transmitted from person to person? 
• Is Ebola being transmitted in a less than lethal form under our eyes without our knowledge?
• Can Ebola be spread by more species of animals than listed under the CDC website?  
• How might Ebola change to become more transmissible to a greater variety of populations impacted by different environmental factors?  How would this risk change if the Ebola virus were to combine with the seasonal flu in a variety of different ways?

Geological Factors

• What factors in Africa are most significant in the etiology of Ebola?  Heat, humidity, coeexistence with and diversity of animal species, alkaline environments, carbon dioxide sequestration and outgassing (e.g. Lake Nyos), the Archaean basement substrate of the West African bedrock, granite, uranium, endospores such as bacillus anthracis, and  natural nuclear fission reactors from underground uranium (Gabon)? 
• What is the impact of the African mining fields?  Iron, gold, lead, silver, arsenic, mercury , uranium and nickel are among products of mining.  Nickel has a positive feedback impact on inflammatory markers. 
• How do endospores such as bacillus anthracis  fit into the story of Ebola, set in the mining context of West Africa, with its iron, gold, silver, arsenic, uranium, nickel and mercury, and the expression of inflammatory markers and feedback indicators?
• Are these various environmental issues constrained to Africa or are they present in other environments, and where do other similar environmental conditions exist?  Do these conditions have to exist in the same place or can an individual experience them by exposure to a variety of locations? For example, Archaean basement layers of rock exist in the Arctic, in Svalbard, which I visited in 2005. How would exposure to Archaea and other factors present in West Africa differ from the situation in Svalbard where it is much colder! Where else can we find archaea and chiral substances?
• How do increases in solar radiation  and changes in the Earth's magnetic field impact the expression of Ebola in Africa? To what extent would these factors affect the expression of Ebola in other areas of the planet?

Environment and Physiology

•  Does the emergence of a disease that promotes bleeding have significance as it relates to climate change or other planetary or environmental factors?    Is some environmental change occurring that would result in blood clotting more easily, something that would need to be countered by less viscous blood and changes in the coagulation cascade?
• How might the environmental factors in Africa affect blood coagulation?  Through mitochondrial regulation as it is impacted by environment, haplogroups and uncoupling in oxidative phosphorylation?  Through the impacts of oxygen reactive species?  Through solar radiation, geomagnetic storms and cycles?  Through the Warburg effect  (which replaces aerobic respiration with glycolysis)? Through arsenic mining?  Through positive feedback mechanisms involving hypoxemia  and inflammatory responses?  
• Is it possible that the Archaean basement layer of rock in West Africa impacts the blood coagulation cascade  and the blood vasculature through chirality?  Would concepts of fractal dimension  and tortuosity explain concepts of blood coagulation and vascular inflammation and other disorders, including stroke and cancers, including those of the blood and lymphatic systems?  
• What impact does the water people drink (and breathe through water vapor) impact people, including the impact on group identity systems and physiological parameters?
• Does the outgassing  of carbon dioxide  as a result of global warming, the release of iron from iron sequestered in the rock, and the release of endospores from sequestration, explain any of the natural events happening today, as regards vascular and coagulation issues?
• Is it possible that Ebola, as a disorder that promotes bleeding, developed as a feedback mechanism to counter the impact of increased blood coagulation due to the environmental impacts raised above? 
•  Bleeding may increase as blood coagulation factors are used up; does Ebola act to promote such bleeding to counter increases in clotting factors secondary to these environmental issues?  Is it possible that Ebola thus impacts the regulatory mechanisms of the coagulation cascade?

Detection

• Could an easy detection test be done for Ebola using, for example, saliva? This might prove less expensive and easier to measure for initial testing prior to full blood workups if it was sufficiently sensitive and specific.
• Could the d-dimer test and PPT tests be used as early indicators of Ebola.
• Can a series of early indicators, including markers of respiratory and coagulation system function and exposure to certain environmental factors, be developed to ascertain risk patterns for specific populations?  
• Where might the solution to Ebola be found?  Only time will tell.  Are lamprey VLR's a potential solution for isolating, detecting, and finding a cure for Ebola, considering their ability to detect bacillus anthracis and their affinity for carbohydrate glycoproteins?  Considering the age of the filoviruses and the characteristics of Ebola itself, is this a potential area to investigate?

Summary

Does the emergence of Ebola reflect the re-emergence of ancient historical patterns?  Have these patterns been carried by reservoir species from the depths of time to the particular victims of Ebola? Will Ebola adapt and spread elsewhere or re-emerge in other parts of the planet, independently?

Are the issues happening in West Africa an early indicator ('Canary in a Coal Mine')  of planetary changes?  These changes include changes in Earth's magnetic field, climate change, global warming and solar radiation, and downstream effects including release of sequestered minerals and gases such as carbon dioxide and methane from rock and oceans.  These are all areas of concern.  Historical examples of changes in Earth's magnetic field are shown over longer periods of time and more recent geologic time periods in this Wikipedia article on the Earth's Magnetic Field.

Finally, I am reminded of the childhood game, "Animal, vegetable or mineral" and associations with the "Tree of Life" (and probably, by extension, "The Tree of Good and Evil").  Ebola is a disease with a past, reflecting deep phylogeny and the rivers of time as embedded in the history of our rocks.

Sources:

marilyndunstan.blogspot.com
Evolution of Adaptive Immunity

Wikipedia:
Ebola virus disease
"The Hot Zone"
Kinshasha Highway
Archaea
Sense (molecular biology)
Messenger RNA
Reverse Transcriptase
Filoviridae
New World Monkey
Lake Nyos
Endospore
Bacillus Anthracis
Natural nuclear fission reactor
Nickel
Chirality
Sunlight
Earth's Magnetic Field
Oxidative Phosphorylation
Reactive Oxygen Species
Geomagnetic Storm
Warburg Effect
Glycolysis
Coagulation Cascade
Fractal Dimension
Tortuosity
Outgassing
Carbon Sequestion
Animal Sentinel
Earth's Magnetic Field-Geomagnetic Polarity
Earth's Magnetic Field-Brunhes Geomagnetism
Earth's Magnetic Field

World Health Organization:
Ebola Virus Disease

CDC:
CDC
Ebola (Ebola Virus Disease
2014 Ebola Outbreak in West Africa (Outbreak Distribution Map)

Phys Org: 
Ebola and Marburg Viruses May be Much Older Than Thought

JoVE Visualize: Anthrax lethal toxin inhibits translation of hypoxia inducible factor 1? and causes decreased tolerance to hypoxic stress

Geology and Mineral Resources of West Africa - The Archaean Basement

National Academy of Sciences: High-affinity lamprey VLRA and VLRB monoclonal antibodies

Berkeley Lab: Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor

NASA Science News - Earth's Inconsistent Magnetic Field

Evolution of Adaptive Immunity

Two Trees (creative digital image)

I attended a "Weiser Endowed Lecture in Immunology" featuring Dr Max Cooper of the Emory University School of Medicine, speaking on "Evolution of adaptive immunity" at the University of Washington in 2012.  Dr Cooper's work is foundational in this subject area.

It is interesting that immunity systems follow a phylogenetic pathway much as the phylogeny of species themselves do. The evolutionary pathway of jawless vertebrates (of whom hagfish and lampreys are surviving members), possess differences in comparison to the common evolutionary pathway followed by other vertebrates.

Lampreys and hagfish do not possess a thymus , nor do they possess a spleen.    Lampreys and hagfish do not possess Major Histocompatibility Complex (MHC) 1 or 2, T-cell receptors or recombination activating genes (RAG 1 and 2) which play an active role in the recombination of T-cell and immunoglobulin  receptors. Lampreys and hagfish posses hematopoietic tissue, the former in the intestine and the latter in the portal vein.  With these changes, the lampreys and hagfish diverged off the common immune system evolutionary pathway prior to the development of certain MHC class immunity in other species.  This is an important benchmark due to the major role that the MHC class plays in vertebrates.  It is a vital aspect which makes the concept of a separate phylogenetic pathway earmarked for the immune system so interesting.  If lampreys do not possess a thymus, then what substitutes in its place?

Lampreys and hagfish utilize a system of leucine-rich repeats )(LRR's) to mediate immune system responses using Variable Lymphocyte Receptor (VLRs), (VLRA's, VLRB's and VLRC's).  The interesting aspect of the jawless vertebrate immune system function is comparing its action in structure and function to the immune systems we are familiar with.  VLRB's have structures similar to toll like receptors (proteins that play a key role in the innate immune system), while their functions are similar to those of antibodies,  and they possess humoral characteristics (using macromolecules in extracellular fluids in immunity systems). They act using discrete populations of lymphocytes (types of white blood cells) .

VLRBs act as an adaptive immune system and can differentiate foreign from self in recognizing lymphocytes.

Lampreys posses a diverse variety of leucine-rich repeats which code for germline and mature genes. They possess a specificity for carbohydrate and protein receptors on bacterial and mammalian cells. They bind antigens with high avidity and affinity, describing the binding capacity of multiple versus single interactions of antibodies with antigenic epitopes.

 In "Evolutionary implications of a third lymphocyte lineage in lamprey", the authors find a thymoid source for VLRA and VLRC assembly in the lamprey gill tips, while VLRB assembly occurs in hematopoietic typhosole and kidney tissues.  VLRC appeared more numerous than VLRA, and predominated in the skin.  They conclude that a similar body plan of two T-cell type lymphocytes in a thymoid type structure and one B-cell type lymphocyte in the blood and kidneys shows some similarity in basic structure to the immune system for jawed vertebrate, while achieving adaptive immunity through different means.

Monclonal VLRB antibodies  from immunized lamprey larvae can recognize plasma cells from myeloma patients.  VLR4, a monoclonal VLRB specific for BclA, the bacillus collagen-like protein, has shown to be specific for B. Anthracis spores.  Information on B. Anthracis can be obtained from the US Centers for Disease Control (CDC) CDC - Anthrax and the World Health Organization (WHO) WHO - Anthrax.

Research indicates a number of applications where VLR's can recognize certain immumogens  An immunogen is any antigen that is capable of inducing humoral and/or cell-mediated immune response rather than immunological tolerance.  These applications include diagnosis, research and bioterrorism investigations.

The Odd Couple: The Mitochondria and the Cell Nucleus

Mitochondrion (Creative Image)

Mitochondria are key to understanding many life processes, in the body, in nature,
and in our environment.

Years ago, the Eukaryotic cell   developed as a symbiotic relationship between a prokaryotic cell and a proteobacteria.  The prokaryotic cell may have been an archaea. The proteobacteria was was incorporated into the cell as an endosymbiont.  As gene transfer took place between mitochondrial DNA  and the cell's nuclear DNA, the extent of the  mitochondrial DNA (mtDNA) decreased and the nuclear DNA incorporated more of the functions performed previously by mitochondrial DNA.  As this occured, the relationship changed from being symbiotic to the development of the mitochondrion as an organelle within the cell.

Much of the work developing the theory of symbiogenesis was done by Lynn Margulis in a 1967 paper..  The theory behind symbiogenesis is a very important topic with wide ranging implications due to the complexities involved in the interoperablity of nuclear DNA and mitochondrial DNA.  These issues are ongoing and represent a major challenge in understanding a wide range of scientific issues confronting our society today.

Mitochondria are present in most living cells that include DNA.  Mitochondria are responsible for  a large portion of the energy generated by the cell.  Mitochondria are responsible for the generation of adenosine triphosphate (ATP) from adenosine diphosphate (ADP)  through aerobic processes using its electron transport chain (ETC).  The energy generated as ATP is many times greater than the energy generated through anaerboic glycolysis, which is an energy generation process that does not use oxygen.

The use by the cell of anaerobic  vs aerobic respiration has significance in studying various physiological processes which occur throughout the body.  These issues have implications in wide ranging areas from cancer to the relationship between sleep and wakefulness.

As energy is generated throughout the body, principles of conservation of energy must be satisfied.  Whether energy is generated through aerobic respiration and Oxidative Phosphoylation (OXPHOS)  using the mitochondrial electron transport chain (ETC), energy generation requires inputs and outputs that must be balanced.  This is a principle called "conservation of energy".  OXPHOS generates ATP,  the "energy equivalent of currency" in the body, energy in the form of heat, and outputs such as oxygen radicals (Reactive Oxygen Species (ROS))  as a byproduct of the process.

Oxygen Canisters

Oxygen reactive species such as superoxide (O-), hydrogen peroxide (H202) and the hydroxyl radical (OH-) can be generated depending upon a number of factors.   This includes natural process in the body involving signaling and homeostasis and also exposure to a number of environmental factors which may increase their generation.  Antioxidants may help the cell counter some of the impacts of reactive species.

Exposure to pollution, chemicals, toxins and radiation may increase oxygen reactive species exposure.  Radiation exposure may include ionizing radiation or non-ionizing radiation  such as cosmic rays  (e.g. gamma rays ).  Geomagnetic storms  and reduced ozone layer  protection at polar regions as Antarctica and the Arctic may increase such exposure, with greater historical ozone depletion  over the Antarctic.

I photographed in Antarctica in November/December 2004, and in October 2006 and photographed in the Arctic in July 2005.  The year 2006 saw the worst levels of depletion (2004 Image-Halley Bay Station, Antarctica) in recorded history.

Cellular processes guide apoptosis, or programmed cell death under a number of circumstances, generating  an intrinsic pathway or extrinsic pathway for cell death.  Reactive species play key roles in this process, as signaling mechanisms, and also in promoting cell death, as free radicals generated by a variety of situations trigger apoptosis.

Mitochondria play a large role in enforcing 'group identity' in a cell. The mitochondria helps to sustain certain energy needs within the body and when certain system parameters (group identity system requirements) are not fulfilled, the process of apoptosis or programmed cell death is intended to kill off certain cells that do not meet those system parameters.

Mitochondria can be loosely or tightly coupled; this means that they can "leak" protons so that more heat is produced (uncoupled) relative to amount of ATP produced;  there are certain uncoupling proteins  that aid in this process, which decreases  the generation of potentially damaging oxygen radicals.  A highly coupled system will thus be more efficient in the generation of energy, less efficient in generating heat, and will generate more oxygen radicals, which can cause damage to the system.  A more loosely coupled system will produce more heat, will generate less oxygen radicals, and will be less efficient in generating energy.  A loosely coupled system will be more valuable in colder climates due to the greater heat protection.  A tightly coupled one will result in more conditions, such as diabetes, which are impacted by the generation of oxygen reactive species.

The generation of reactive oxygen species is a significant issue in DNA damage  and mutations involving mutagenesis.  Mitochondrial DNA (mtDNA) are much less protected from the generation of reactive species than nuclear DNA.  In the proverbial sense, they sit at the edge of the  oxidative phosphorylation 'fiery furnace' and absorb more damage than nuclear DNA.  Nuclear DNA has greater protection from reactive species, being protected by histones   and telomeres.

Mitochondria can be damaged by reactive species, however, there is a certain amount of punishment that mitochondria can take before a process called heteroplasmy  takes place. Heteroplasmy in the mitochondria is a process where, due to mutation, mitochondrial damage or other process, more than one mitochondrial genome can exist.  This process may be associated with mitochondrial disease and be more extensive the greater the degree of heteroplasmy.  However some individuals may live to long ages with some degree of heteroplasmy.

There is a basic problem with mitochondrial damage and mutation in so far as the mtDNA and the nuclear DNA interoperate in the OXPHOS process.  This is because, as mentioned earlier in the article, some mitochondrial functions ages ago were shifted into the nuclear DNA through the process of gene transfer.  Cytochrome C belongs to the cytochrome c family of proteins and is an integral part of the ETC.  Cytochrome C has a long history, which goes back to time periods when the Earth was subject to heavy amounts of radiation.  Illnesses associated with Cytochrome C may involve both nuclear DNA and mitochondrial DNA.

Since Nuclear DNA has greater protection than mitochondrial DNA (mtDNA) from the insult of reactive species, the degree of damage in each case will differ, or in the case of nuclear DNA, there may be minimal or no damage.  This will lead to interoperability issues as mutations and damage occurs. Interoperability is the ability of systems to work together.  As oxidative stress occurs at different rates and to different but  inter-operating parts of the cell (mtDNA and nuclear DNA), illness and damage occurs, and potentially mutations.  This occurs in systems requiring heavier use of energy, including muscles.  Respiratory muscles bear the burden of oxidative stress, as these muscles are those subject to the greatest use during sleep.  Sleep apnea may be associated with higher levels of exposure to oxidative stress.

As we are subject to greater and greater levels of substances that create oxygen reactive species, we can see that problems can add up.  There are greater and greater chances of damage and mutations, the probability of heteroplasmy increases, the levels of heteroplasmy in the cell may come closer to the levels of heteroplasmy that may be tolerated in the cell without incurring mitochondrial disease.

We can see, therefore, that exposure to reactive species such as environmental toxins and radiation may provide for mutations in both nuclear and mitochondrial DNA, that these processes may occur at different rates, and that past a certain point, mitochondrial disorders may develop as the result of such exposure. At the same time, mutations that are beneficial may sometimes occur, and mutations and damage that are harmful may indeed result.  The ability for mutations that are adaptive to occur may reflect the ability of the mitochondrial DNA and the nuclear DNA to inter-operate, which is statistically difficult, considering the conditions under which each of these processes work.

Thus any process which seeks to advance a species by introducing mutagenic factors via the use of the creation of oxygen radicals must take into consideration that mutations and damage may result in the process and that individuals may be harmed in such process.  Due consideration must exist for who is subject to such exposure, and when the risk of subjecting certain individuals to such exposure constitutes a material risk that makes such experimentation untenable in  a civilized society.

 The risks of exposure to reactive species increases with the degree and length of the exposure, impacting the risk of early morbidity and mortality. Mutagenesis is more effective when it occurs in germ line cells which can pass mutations, either favorable, or unfavorable on to the next generation

Where such experiments are conducted, they must be conducted in an ethical fashion, they must be done with full informed consent of those involved, they must adhere to the law of civilized nations, and the ongoing experience of such studies must be monitored and measured so that those involved are not unduly harmed and the patient population put at excessive risk.

It must be made abundantly clear that if our society depends upon mutations to adapt the species to future environmental (or other) challenges, that those who have been subject to environmental (or other) assaults for such purpose be treated with due respect, that their contributions be valued, and their condition be measured, monitored and treated. It is clear that what these individuals are doing on a collective basis is aiding the future development of humanity. They are test subjects in a process that will benefit others, later.

What are our future ecological and planetary challenges and how can we adapt to them?  How do these challenges impact our exposure to environment risks and how we deal with them?  These are all important issues.

The mitochondria, as a vital cog in the production of energy has a very important part of the story that must be told as we seek to deal with the environment, climate change and other planetary challenges that we face.

Leptin

Butter

I attended a lecture in 2008 about leptin signaling given at Harborview Medical Center through their research programs on diabetes, metabolism and obesity.  The lecture, although highly technical, was  interesting and it gave me plenty to think and read about.

Leptin is what is called a signal transducer.  A signal transducer is an extracellular  signaling molecule that activates a receptor inside or on the cell surface, initiating a series of events, biochemical reactions.    Leptin signaling is involved in a number of areas relating to the management of energy throughout the body, regulating or giving permission for the use of energy for a variety of vital functions.  As I read more about leptin, it led me into a labyrinth of other, associated issues.

Leptin is involved in signaling relating to mesolimbic (dopaminergic) reward centers, food, satisfaction, glycemic control, saiety and reproduction.  Leptin deals with long term energy storage, provision of energy to the brain and gives permission for the use of energy falling within its defined duties.  Intuitively, one wonders what happens if energy demands are requested for things that aren't associated with its associated duties.

Leptin acts to communicate to the Central Nervous System the availability of energy stores.  It acts to restrain food intake and induce energy expenditure, when necessary.   Leptin acts with other systems, such as the Sympathetic Nervous System,  and with factors such as thyroid hormone  and insulin,  in regulating energy use throughout the body and in insuring the thermodynamic  efficiency of skeletal muscle, for example.  Leptin is also involved involved in the cardiovascular system, for example in cardiac hypertrophy.

Leptin is increased, or up-regulated, in obese people.  It increases appetite, generates a low metabolic rate, decreases thyroid function and is impacted by sleep apnea  issues.  Dysregulation of leptin adversely impacts fertility.  Leptin acts on lipid and glucose metabolism.  Leptin also regulates bone metabolism.  This may serve to improve structure with increasing weight by regulating the allocation of higher density bone development.    Leptin resistance occurs during obesity when increasing leptin levels do not have an impact.

Leptin acts in the brain in a neuroprotective  fashion that may also impact memory.  Leptin may be necessary to protect the cell against cell death (apoptosis).

Leptin plays a key role in thermoregulation, working through diverse systems such as the brain's preoptic area and hypothalamus.  Studies in the brown adipose tissue (BAT)  of mice injected by virus indicated involvement of leptin in regulating BAT circuits.  Severely obese mice that lack leptin or its receptor show decreased BAT thermogenesis, and are thus challenged to maintain their body temperature and adapt to cold temperatures.

Leptin may be a key component in considering survival issues under a variety of scenarios or projections associated with climate change modeling.  It may react to a variety of seasonal (zeitgeber) cues, as well as sexual cues regarding melatonin , odor and reproduction.  It will react to hedonistic feelings regarding food, appetite and to the allocation of resources regarding shorter term versus longer term energy needs.

Leptin plays its role along with a host of other players in this complicated web of life.

Book Review:
Group Immunity Systems

 "From Bacteria to Belief: Immunity and Security by Dr Luis P. Villarreal, UC Irvine
in "Natural Security, A Darwinian Approach to a Dangerous World"
edited by by Raphael D Sagarin and Terence Taylor

Fractal Julia Design (creative digit image)

I attended a guest lecture by Dr Luis Villarreal, University of California, Irvine, given at the University of Washington . Dr Villarreal gave a very interesting talk about viruses, which got me interested in reading some of his work on the role of viral evolution in life.

Dr Villarreal's work appears in,  "Natural Security, A Darwinian Approach to a Dangerous World" Edited by Raphael D Sagarin and Terence Taylor.  The book discusses applications of security systems which exist in  evolutionary biology,  to solve security based problems in the risky world that we humans have to deal with.  In this blog post I discuss Dr Villarreal's article, in which he discusses immunity systems.  

Dr Villarreal develops his concept of group immunity based on bacterial models, discussing the colonization of genetic parasites such as viruses.  Systems bind individual units to the group using a "carrot or stick" approach to enforce group identity.   His model employs the term Addiction Model for this approach.  This model uses the term "antitoxin" for protective aspects of the system which draw and retain members, and "toxin" for aspects which are destructive or harmful to nonmembers or members who violate the group identity system rules. Together these aspects constitute a security system which is the basis for his discussion.

Biological based concepts are extended to higher level human biological models by asking how we identify members of a group, how we identify self versus foreign entities and how we respond to threats. Human cognitive sensory systems using visual or pheromone based cues are employed.   

Dr Villarreal tackles the very difficult topic of death of the individual for the good of the whole in the context of programmed cell death (apoptosis) where many cells must die in the process of developing a specific specialized tissue, giving specific biological-based examples.   He discusses the issue of genetic parasites which create an addiction state within a host cell whereby the host cannot lose the parasite and still remain alive.  Competition between group identity systems is also important as Dr Villarreal discusses how group identity systems may kill off individual E. Coli cells if one of them is co-opted by another organism.   

Dr Villarreal goes on to discuss adaptive immune systems.  He discusses the worm C. Elegans, whose neural system and ability to protect against endogenous retroviruses is of evolutionary interest.  He discusses the recognition of self versus foreign, the reigning in of an over-reactive immune system that erroneously attacks itself,and the development and training of group identity.  He discusses how evolutionary features of the immune system can be extended to the social activity of humans based on long standing biological evolutionary principles.

Dr Villarreal discusses the creation of a stable group identity system using sensory based systems that may exclude input from non-members.   "Colonization" and imprinting (of language or group identity) is described as a process through which group identity is established and maintained.  The assignment of meanings to words, through language, and the stability of memories are important in such systems.

Dr Villarreal's work is an interesting discussion of the use of evolutionary biology techniques applied to the phylogenetic "tree of life" and one is left wondering the extant implications for the "tree of the garden of good and evil".  

"Natural Security, A Darwinian Approach to a Dangerous World" can be found  through the California Scholarship Online and on Amazon, with interesting contributions from a variety of authors on the topic of natural security and biological based models.

Fractals 

Portion of a Mandelbrot Set

A fractal is an entity that exhibits a repeating pattern.  Many patterns in nature exhibit fractal phenomenon and computer simulations are used to generate fractal patterns artificially.  Natural phenomena such as coastlines  exhibit a fractal pattern, as the pattern displayed may be exact (self-similar) or perhaps just similar at various levels of detail or magnification.  Snowflakes and trees property of continuing detail at higher levels of magnification.  Because of this, fractals are considered "nowhere differentiable" because of their inability to be measured traditionally.

Fractals are used in many fields, including physics, biology, medicine and physiology, imaging and financial fields. Fractals may apply in economic contexts such as the stock market Standard and Poors 500 Index, when examining longer term patterns (years) vs shorter terms (months, days, intra-day trading).  Fractals may be used in cinema, advertising, graphic design and climate science .  Fractals are a beautiful representation of art in their own way, in the visual arts, including the Droste effect, which is a picture within a picture. 

Fibonacci numbers, the basis of the Fibonacci Sequence appears in fractal geometry in a wide variety of ways.  Fractal dimension is a measure used to quantify complexity.  It measures  how detail changes with scale and the capacity of the fractal to fill space.  Various definitions of fractals and mathematical indicators exist, including a definition by mathematician Benoit Mandelbrot  who characterized a fractal as an object whose Hausdorff-Besicovitch dimension  is greater than its topological dimension. 

Wikipedia lists the Hausdorff-Besicovitch dimensions of a number of common fractals, including the Koch snowflake, Sierpinski Triangle, Quadric Cross, Julia Set and the Boundary of the Mandelbrot Set. Values for natural processes such as  the Coastline of Ireland , Great Britain and Norway are listed, as are values for various Brownian motion and random walk processes.  Dimensions are shown for biological models such as Cauliflower, Broccoli, the surface of the Human Brain , and the Human Lung.  Higher numbers indicate increasing complexity.

Fractals may be use in diagnostic medicine and physiology.  For example, blood vessels may exhibit fractal characteristics, as may the lung and surface of the human brain.  Tortuosity, another metric, relates the ratio of the actual length of a curve or segments of a curve to the distance between the two ends. Tortuosity may also reflect the degree to which a curve crosses over itself.  
  
Tortuosity was used for characterizing animal trails of mites  with regards to Brownian motion pathways.  Fractal dimension and tortuosity may both be used in measurement of blood vessels, as is shown in this article from the medical journal PubMed in a study of pulmonary hypertension.  In that study, distance metric, a measurement of tortuosity, was statistically more significant than the fractal dimension in correlating clinical patient parameters with the particular metric.   This goes to show that the use of different metrics may produce differing correlations, perhaps a clue in itself to underlying characteristic studied.

Fractals  form the basis of many aspects of life and the world around us, igniting our curiosity, aiding our research, informing us, and conveying a sense of beauty, form and function.

The Ginko Biloba Tree

Ginkgo Leaf Fossil, Burke Museum, University of Washington, Seattle, Washington

The above photo of the Ginkgo Leaf Fossil was taken at the Burke Museum, University of Washington, Seattle, Washington and  represents a fossil of a Ginkgo taken in Smithers, British Columbia, Canada.  Driftwood Canyon Provincial Park, in Smithers, is one of the world's most significant fossil beds.   

The Ginkgo Biloba tree appears naturally, in the wild, only in China.  It is grown in many place worldwide, as a cultivated tree, and adapts well in well watered and well drained habitats. Ginkgo Biloba is a living fossil , dating back 270 millions to the Permian Period  .  Ginkgo has managed to evolve along a very long evolutionary time period without much speciation.

It is an interesting example of a plant that has had extreme longevity, slow growth, late reproductive maturity and has survived through many diverse and disturbed environments, including the Ice Age .  It has  managed, despite  a narrow base of speciation to support it.  It has two sexes, male and female, and has its ability to exhibit clonal reproduction, a process which produces a population of identical units which reproduce from the same ancestral line. This has helped it survive evolutionary challenges.  The Ginkgo is also highly resistant to air pollution and grows in areas where air pollution has damaged other species.

A HHMI BioInteractive presentation discusses the issue of clonal reproduction in a video. "Are Males Really Necessary?"  using fruits and vegetables as props.   The video is thought provoking and uses creative use tools to discuss an educational subject.  The 23rd or "sex chromosome"  is a specialized area of interest not explicitly discussed.  Protocols for tossing out wilted lettuce or black bananas present an analytic challenge.

The black banana we consider tossing out might be more useful than the newest banana, especially if we are considering  baking banana bread to bring to the next potluck.  It takes awhile to produce the necessary senescence in a banana to get the right flavor and texture for banana bread.  Thus,  Interoperability, whether it be in bread making, computer engineering or other systems, is an important evolutionary issue, involving mutations along with a stochastic process.

One has to wonder at the combination of processes that has sustained the Ginkgo for million years as well as the diverse environments that the Ginkgo tree  has experienced.   Ginkgo is an herb.  Its leaves and sometimes its seeds are used to make extracts for medicinal purposes, including memory disorders such as Alzheimers and dementia.  Even as we consider the marvel that is the Ginkgo Biloba, we find fascination and beauty in its foliage, and comfort in the shade that it produces.  It is a tree and much more.